Nattō’s Nutritional and Epigenetic Health Benefits by Ben Lynch (2019)

Japan has a famously long average life expectancy.  In 2017, Japan had the second longest average life expectancy in the world at 85.30 years, following only Monaco (89.40 years) which could arguably be removed from the list based on its extremely small size (population of 38,695).[1] Compare this to the United States, which humbly comes in 43rd with an average life expectancy of 80.00 years. Life expectancy results from countless factors – political system, healthcare system, access to medicine, education, climate, status of the economy, and level of physical activity to name a few – and to imply that a single factor dictates life expectancy would be simply untrue. It is important to note, however, that nutrition and diet arguably has the strongest impact on life expectancy. The relationship between nutrition and life span has been studied extensively over the years, and many famous papers have firmly concluded that “nutrition is a primary determinant of lifespan” (Weindruch and Walford 1982; Chippindale et al. 1993; Good and Tatar 2001; Walker et al. 2005; Fontana et al. 2010).[2]

Over the last few decades, Japan’s population age composition has been skewed upwards.  In other words, Japan has a very large elderly population.[3] As this population continues to age, the wellbeing of the elderly has become a priority to the government. Japan created the National Food Research Institute (NFRI), a branch of the National Agricultural Research Organization (NARO), partially to support this large aging population.[4] One of the major goals of the NFRI was to conduct scientific analysis on various foods to quantitatively determine which foods yield actual health benefits to support their aging population. In addition, they wanted to discover the molecular mechanisms underlying a food’s ability to extend and improve quality of life.[5] One of the foods that they have honed in on is nattō. Scientists at the NFRI have published many papers confirming the numerous health benefits of nattō and they have been encouraging citizens to eat more of this fermented soybean dish. Their research suggests that the consumption of nattō is a significant factor in extending Japan’s average life expectancy at both an individual level and even across generations.

 

Over the last few centuries, Japan has maintained an obsession with neba neba.  Translating to “slimy” or “sticky”, these foods have a unique texture most Americans find repulsive. Although many foods are described as neba neba, nattō is the most famous and one of the most commonly eaten. Nattō is a fermented soy bean dish most commonly eaten for breakfast, but also consumed during other meals, as a snack, or as an ingredient for other dishes such as soup. Nattō is prepared by washing soy beans, soaking them in water, placing them in boiling water, and then adding Bacills subtilis (nattō) spores.[6] These spores are resistant to the high temperature so the boiling water kills all other microbes and leaves only the desired B. subtilis bacteria6.  The soybeans are then kept incubated for 16-24 hours to allow B. subtilis to partially digest the soybeans and drive alkaline fermentation. The B. subtilis secretes a polymer biofilm made of γ-glutamic acid which protects the bacteria and gives nattō its slimy, stretchy consistency. When consumed, this biofilm shreds glutamate molecules which the tongue detects as umami, giving nattō its unique, rich and distinctive taste (which even many Japanese, particularly in the south, find repulsive).[7]

 

Individual Health Benefits of Nattō

Researchers at the NFRI have uncovered and documented many health benefits to eating nattō. Even before fermentation, soybeans contain many beneficial functional components such as dietary fibers, lectins, metals, isoflavones, unsaturated fatty acids, polyphenols, and vitamins.6  Soybeans are also rich in protein and researchers have found that the absorption rate of protein (labeled by nitrogen) from ingesting nattō was 83.6% compared to an 81.0% absorption rate for soybeans boiled without B. subtilis fermentation. B. subtilis releases proteases that break down soybean proteins into smaller, digestible amino acids which allows for increased protein absorption. This feature is notable as soybeans can be hard to digest, and nutrients are only as good as they are utilized by the body.

Additionally, B. subtilis is able to digest insoluble fibrin in soybeans by secreting a serine protease enzyme called nattokinase. Fibrin is also formed during the clotting of blood in the human body. During the clotting process, this insoluble protein is generated to form a fibrous mesh to impede blood flow.[8]  Researchers have discovered that nattokinase could potentially be used as a thrombolytic enzyme to treat thrombolytic diseases such as deep vein thrombosis. In other words, nattokinase could be used as a blood thinner, working to break down blood clots and reduce the risk of heart disease and stroke. Nattokinase intravenous injections in rats have been shown in lab to effectively degrade chemically-induced thrombosis. Another research group found that healthy adults who consumed 200g of nattō for breakfast daily showed increased fibrinolytic activity, which is the body’s natural system that prevents blood clotting. When these same participants took an additional regiment of purified nattokinase enzyme on top of their nattō breakfast (1.3 g taken 3 times per day), their fibrinolytic activity increased further and there was an increased level of degraded fibrin products in serum.[9] Multiple studies have shown that eating nattō and taking concentrated nattokinase supplements effectively increases the fibrinolytic system. Human clinical trials are still ongoing to investigate the safety and efficacy of more aggressive nattokinase enzyme therapy to treat thrombolytic diseases in hospitals, which could replace the current commercial thrombolytic enzymes such as warfarin, which are expensive and have negative side effects. Currently, lower concentration blood thinning nattokinase supplements are available for purchase and are fast gaining popularity.

Researchers have also found that ingesting nattō yields probiotic effects that further enhance this humble food’s complex profile. The human gut is teeming with a complex community of microorganisms and this microbiome is hugely important in modulating digestion, immune response, the production of vitamins, and regulating metabolism.[10]  Eating nattō introduces B. subtilis to the gut, which is beneficial to microbiome composition and health. One study found that the oral administration of B. subtilis or nattō in adults increased Bifidobacterium concentration (good bacteria) in feces and decreased lecithinase-positive clostridia concentration (bad bacteria) in feces (Terada et al. 1999). Interestingly, these changes in feces bacteria composition was not observed in adults receiving oral administration of boiled soybeans that were enzymatically digested to simulate nattō digestion. This suggests that ingestion of the B. subtilis bacterium is responsible for this probiotic effect, and the probiotic health benefit is specific to nattō.

On top of the probiotic and fibrin-dissolving qualities, superfood nattō also has antitumor properties. Researchers found B. subtilis exhibited effective antitumor activity against Ehrlich carcinoma cells. One research group injected Ehrlich carcinoma cells into the groins of mice and then injected B. subtilis in the same area two days later. They found that there was a statistically significant decrease in tumor weight in the mice receiving the B. subtilis injection as compared to the tumors in the control mice. In addition, all of the control mice receiving the Ehrlich carcinoma cell injections died within 16 days whereas 65% of the mice also receiving the B. subtilis injection survived for 35 days or longer. Another research group found that B. subtilis injections inhibited the activity of a common tumor promotor, phorbol acetate, as was measured through a dye-transfer technique. Cells treated in vivo with phorbol acetate showed a significantly reduced transfer of dye through cell gap junctions (a phenomenon common to tumor formation). Cells that were then treated with B. subtilis showed a recovered increase in gap junction dye transfer. This antitumor activity was found to be mainly driven by a saturated hydrocarbon called hentriacontane. This hydrocarbon is not found in either soybeans or in B. subtilis so researchers are confident it is produced by the fermentation process involved in making nattō, meaning this antitumor property is unique to natto. They also concluded that one standard package of nattō contains enough hydrocarbons to effectively prevent the promotion of tumors.[11]

Another beneficial compound nattō offers in relative abundance is vitamin K2. According to Dr. Dennis Goodman, a Professor of Medicine at New York University, vitamin K2 is the most important vitamin for people to be aware of since “most people are not getting nearly enough K2 in their diet.”[12] Nattō just happens to be the most potent food source of vitamin K2. The main function of vitamin K2 is aiding in the direction and transport of calcium to the correct areas in the body. It prevents calcium from entering the kidneys where they can collect and cause kidney stones, and from entering blood vessels where it increases the risk of heart disease.[13]  Vitamin K helps direct calcium towards bone and teeth, making them strong and resistant to cavities respectively. A study found that there are statistically significant lower rates of osteoporosis in eastern Japan as compared to western Japan since nattō is consumed in much higher quantities in eastern Japan.[14] Another observational study found that Japanese women who ate at least two servings of nattō weekly have statistically significant higher levels of vitamin K2 in their blood and experienced far fewer hip fractures than age-matched European women.[15] Nattō contains over 300 micrograms of vitamin K2, which is over seven times the daily suggested minimum. According to Dr. Goodman, “the only food that gives you a sufficient amount [of vitamin K2] is nattō.”[16]

 

Generational Health Benefits of Nattō

In addition to the numerous health benefits obtained through the individual consumption of natto as described above, there are also epigenetic changes that result from natto consumption that benefit both the individual and an individual’s future offspring.

Epigenetics refers to changes in organism phenotype resulting from changes in gene expression, without changing DNA sequence.[17] These modifications most often change gene expression through DNA methylation and histone modification. Unlike the genome, the epigenome is not fixed; rather it changes over time naturally as we age and in response to environmental changes. Since epigenetic changes affect the expression of genes, changes to the epigenome can alter the functions of cells and tissues and thus increase or decrease the risk of disease. It is commonly accepted that nutrition interacts closely with gene expression via epigenetic modulation.[18] It is understood that short-term changes in gene expression as a response to diet result primarily from transcription factors whereas longer-term responses involve changes in epigenetic factors. There has been substantial empirical evidence from many human studies of the association between diet and epigenetics and many in vitro and animal studies have shown a causal relationship between nutrition and epigenetic markers (Mathers et al. 2010). Interestingly, butyrate (a short-chain fatty acid) was one of the earliest discovered epigenetic modifiers, working by inhibiting histone deacylation and thereby maintaining chromatin in a more open configuration (Candido et al. 1978). Butyrate is an end product in the fermentation of dietary fiber and other carbohydrates and is produced by B. subtilis in nattō. Many of the beneficial health benefits gained from ingesting nattō, as described above, result from the addition of beneficial proteins, enzymes, and bacteria to the body. Moreover, many of these health benefits continue while not actively digesting natto because of epigenetic changes. Nattō contains molecules that, when digested in the body, can travel to the nuclei in body cells and alter long-term gene expression, allowing for these health benefits to last days to weeks after eating nattō. A regular diet of nattō would alter gene expression in more cells and for a longer duration, allowing these positive health benefits to be enjoyed for a longer time.

Interestingly, epigenetic changes can be hereditary and passed down to offspring. Although there is some controversy over the matter, numerous studies have found that the diet of parents and grandparents influences the phenotype of the current generation through hereditary changes to the epigenome (Pembry et al. 2006, Miska & Ferguson-Smith 2016).[19]  Eating nattō alters the epigenome and therefore extends the health benefits not only for the individual, but also for their offspring.

 

Conclusion

Scientists at the NFRI and around the world have conducted numerous studies confirming the many health benefits of eating nattō. Eating nattō can reduce the risk of blood clotting and therefore heart disease, promote a healthier intestinal microbiome, fight tumor production, and help build stronger bones and teeth from introducing nattokinase, B. subtilis var. natto bacteria, vitamin K2, and other molecules found in nattō into the body. These health benefits are extended in and enjoyed by individuals through epigenetic changes resulting from eating nattō, especially if made a consistent portion of the diet. Eating nattō not only provides an individual with health benefits but can also benefit the health of an individual’s offspring. Nattō has been a common dish in Japan for at least hundreds of years. Thus the widespread consumption of natto over a long period of time in Japan is a major reason for the extremely long average Japanese life expectancy.

 

[1] “COUNTRY COMPARISON :: LIFE EXPECTANCY AT BIRTH.” Central Intelligence Agency, Central Intelligence Agency, www.cia.gov/library/publications/the-world-factbook/rankorder/2102rank.html.

[2] Christina May, et al., “The effect of developmental nutrition on life span and fecundity depends on the adult reproductive environment in Drosophila melanogaster,” Ecology and evolution, vol. 5.6 (2015): 1156–68.

[3] “Japan Age Structure,” www.indexmundi.com/japan/age_structure.html.

[4] https://www.naro.go.jp/english/laboratory/nfri/index.html

[5] “Food Research Institute, NARO.” IAM/NARO: Electronic Control Unit Certified by ISOBUS, www.naro.affrc.go.jp/english/laboratory/nfri/index.html.

[6] All references to B. Subtilis in this paper will henceforth refer to this specific nattō variety.

[7] Nagai, Toshirou.  “Health Benefits of Fermented Foods and Beverages.” Google Books, books.google.com/books?hl=en&lr=&id=RJC9BwAAQBAJ&oi=fnd&pg=PA433&dq=natto%2Bbenefits&ots=CFTtFLWKOq&sig=nXSfeQcZMDbLqMW4cbiStaY_Hdo#v=onepage&q=natto%20benefits&f=false.

[8] Litvinov, Rustem I and John W Weisel, “What Is the Biological and Clinical Relevance of Fibrin?” Seminars in thrombosis and hemostasis vol. 42.4 (2016): 333–43.

[9] Ibid.

[10] “Gut Microbiota Info.” Gut Microbiota for Health, www.gutmicrobiotaforhealth.com/en/about-gut-microbiota-info/.

[11] Nagai, Toshirou.  “Health Benefits of Fermented Foods and Beverages.”

[12] Schiffman, Richard. “Are You Ready to Eat Your Natto?” The New York Times, The New York Times, 2 Aug. 2016, well.blogs.nytimes.com/2016/08/02/are-you-ready-to-eat-your-natto/.

[13] Stata, et al. “The Ultimate Vitamin K2 Resource.” Chris Masterjohn, PhD, 17 Jan. 2017, chrismasterjohnphd.com/2016/12/09/the-ultimate-vitamin-k2-resource/.

[14] https://well.blogs.nytimes.com/2016/08/02/are-you-ready-to-eat-your-natto/

[15] Nagai, Toshirou.  “Health Benefits of Fermented Foods and Beverages.”

[16] https://well.blogs.nytimes.com/2016/08/02/are-you-ready-to-eat-your-natto/

[17] Weinhold, Bob. “Epigenetics: the science of change” Environmental health perspectives vol. 114,3 (2006): A160-7.

[18] Malcomson, F. C. and Mathers, J. C. (2017), Nutrition, epigenetics and health through life. Nutr Bull, 42: 254-265. doi:10.1111/nbu.12281

[19] Ibid.