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- Natto for Brain Health Too!
- While investigating the potential brain health implications of eating soy-based natto alluded to by Michael, I came across some addition information, that not only suggests natto may not be bad for brain health, but might actually be downright good. Here is what I found.
- Apparently Vitamin K2 (MK-7 form) isn't the only potential beneficial component of natto. Natto contains Nattokinase (henceforth referred to as NK), which is a serine protease, or in other words, an enzyme that cleaves protein bonds. Now obviously, cleaving proteins could be a good thing, or it could be a bad thing. But in the case of NK, it looks to be a good thing.
- But first you might ask - don't ingested enzyme's get broken down in the digestive system? Why think NK would make it intact to the bloodstream from eating natto? The answer is found in study [1]. Short answer, in healthy human volunteers, a single dose of orally ingested NK, in softgel form, raised NK level in serum. NK level in the blood was elevated during a period from 2 to 24 hours post ingestion. The amount of purified NK in the single oral dose (2000 FU, or about 100mg NK) used in this study was about equivalent to amount of NK in 50g of natto. Based on unit conversion (from CU's to mg's) from studies [1] and [2], there is about 50mg of NK in the 25g of natto I eat per day.
- So with that out of the way. What does NK do?
- Apparently a heck of a lot. For a thorough discussion, with references, see these two extensive and very informative webpage on NK and this one too. A few excerpts from these two web pages:
- Heart disease
- First, in addition to the artery calcification prevention benefit of MK-7 discussed in my first post, NK may be potentially useful as a clot-buster and blood thinner, There is quite a bit of evidence for its effectiveness in this regard[9][10][11][12][13][14][15][16][17]. Here is a typical result from amongst these studies [3], in which subjects were given a dose of NK equivalent to 50mg of natto:
- As a result, D-dimer concentrations at 6, and 8 hours, and blood
- fibrin/fibrinogen degradation products at 4 hours after NK administration
- elevated significantly (p < 0.05, respectively). Factor VIII activity declined at
- 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was
- higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial
- thromboplastin time prolonged significantly at 2 and 4 hours following NK
- administration (p < 0.05 and p < 0.01, respectively). All the changes, however,
- were within the normal range. In conclusion, thus, a single-dose of NK
- administration appears enhancing fibrinolysis and anti-coagulation via several
- different pathways simultaneously.
- But possible side effects have been reported. In one case report, a patient concurrently taking aspirin and 400 mg of nattokinase daily (equivalent to for seven consecutive days to prevent stroke suffered an acute cerebellar hemorrhage.[18]
- Blood Pressure
- One human intervention using nattokinase at an oral dose of 2,000 FU per capsule once daily (equiv to 50 g natto / day) for 8 weeks in persons with hypertension (n=86) noted that nattokinase was associated with a reduction in systolic blood pressure of 5.55mmHg (95% CI of 0.57-10.5mmHg reductions) and diastolic blood pressure by 2.84mmHg (95% CI of 0.33-5.33mmHg) with a decrease in renin activity by 1.17 ng/mL/h.
- ---------
- [1] Altern Ther Health Med. 2013 May-Jun;19(3):16-9.
- A pilot study on the serum pharmacokinetics of nattokinase in humans following a
- single, oral, daily dose.
- Ero MP(1), Ng CM, Mihailovski T, Harvey NR, Lewis BH.
- CONTEXT: Nattokinase is a serine protease and is derived from natto, a
- traditional Japanese, fermented, soybean food meal. Multiple authors have
- described the significant fibrinolytic, antithrombotic, and antihypertensive
- effects of natto. Nattokinase has been growing in popularity for use as a dietary
- supplement for the benefit of cardiovascular health. Little is known regarding
- the pharmacokinetic and pharmacodynamic properties of this enzyme, and the
- bioavailability of nattokinase is currently unknown.
- OBJECTIVE: This study intended to (1) detect nattokinase directly and
- immunologically, (2) show that nattokinase and/or its metabolites were detectable
- in human blood following ingestion of a commercial preparation, and (3) chart a
- pharmacokinetic dosing effect for nattokinase.
- DESIGN: The research team designed the pilot study as an in vivo, human clinical
- trial. Healthy human subjects responded to an advertisement and were screened.
- Subjects who satisfied both inclusion and exclusion criteria were enrolled into
- the study. Subjects were then instructed to orally ingest a single capsule
- containing a known concentration of nattokinase immediately following a baseline
- blood draw. Subsequent blood draws occurred over a 24-h period.
- SETTING: This study was conducted in Oakland, California, at a clinical reference
- laboratory and was performed with the approval of an institutional review board
- (IRB) to ensure that appropriate ethical standards were met.
- PARTICIPANTS: Eleven healthy participants (five male, six female, ages 21-65),
- who met eligibility criteria, were enrolled.
- INTERVENTION(S): Administration of nattokinase occurred orally with the ingestion
- of a single daily dose (2000 FU) of nattokinase. Capsules, each containing
- approximately 100 mg of nattokinase, in softgel form (NSK-SD, Japan Bio Science
- Laboratory, Osaka, Japan), were used in the study.
- OUTCOME MEASURE(S): Baseline blood samples were collected, and participants were
- observed swallowing a single capsule of the nattokinase supplement before
- returning at 2, 4, 8, 12, 24, and 48 h post ingestion for subsequent blood draws.
- The presence of nattokinase in serum was measured by an enzyme-linked
- immunosorbent assay (ELISA), using a rabbit, polyclonal, antinattokinase-capture
- antibody. A pharmacokinetic pattern was observed for nattokinase between baseline
- and 48 h postdose.
- RESULTS: Peak serum levels of nattokinase were observed at approximately 13.3 h ±
- 2.5 h (mean ± standard error) postdose. Statistically significant increases in
- binding were detectable from baseline when comparing averaged data at time points
- t = 2 h-t = 24 h.
- CONCLUSIONS: These results provided the first evidence that nattokinase can be
- measured directly in the blood of humans. The results further suggest that a
- larger, more extensive, pharmacokinetic study of nattokinase is warranted.
- Additionally, looking for intact enzyme and bioactive nattokinase peptides should
- be a consideration for future studies investigating the pharmacokinetic profile
- of nattokinase.
- PMID: 23709455
- [2] Experientia. 1987 Oct 15;43(10):1110-1.
- A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a
- typical and popular soybean food in the Japanese diet.
- Sumi H(1), Hamada H, Tsushima H, Mihara H, Muraki H.
- Author information:
- (1)Department of Physiology, Miyazaki Medical College, Japan.
- A strong fibrinolytic activity was demonstrated in the vegetable cheese Natto,
- which is a typical soybean food eaten in Japan. The average activity was
- calculated at about 40 CU (plasmin units)/g wet weight. This novel fibrinolytic
- enzyme, named nattokinase, was easily extracted with saline. The mol. wt and pI
- were about 20,000 and 8.6, respectively. Nattokinase not only digested fibrin but
- also the plasmin substrate H-D-Val-Leu-Lys-pNA (S-2251), which was more sensitive
- to the enzyme than other substrates tried. Diisopropyl fluorophosphate and
- 2,2,2-trichloro-1-hydroxyethyl-o,o-dimethylphosphate strongly inhibited this
- fibrinolytic enzyme.
- PMID: 3478223
- -----------
- [3] Sci Rep. 2015 Jun 25;5:11601. doi: 10.1038/srep11601.
- A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation
- profiles.
- Kurosawa Y(1), Nirengi S(1), Homma T(1), Esaki K(2), Ohta M(3), Clark JF(4),
- Hamaoka T(1).
- Our aim was to determine the quantitative effects of a single-dose of Nattokinase
- (NK) administration on coagulation/fibrinolysis parameters comprehensively in
- healthy male subjects. A double-blind, placebo-controlled cross-over NK
- intervention study was carried out in 12 healthy young males. Following the
- baseline blood draw, each subject was randomized to receive either a single-dose
- of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with
- subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6
- and 8 hours following administration for analysis of coagulation/fibrinolysis
- parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood
- fibrin/fibrinogen degradation products at 4 hours after NK administration
- elevated significantly (p < 0.05, respectively). Factor VIII activity declined at
- 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was
- higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial
- thromboplastin time prolonged significantly at 2 and 4 hours following NK
- administration (p < 0.05 and p < 0.01, respectively). All the changes, however,
- were within the normal range. In conclusion, thus, a single-dose of NK
- administration appears enhancing fibrinolysis and anti-coagulation via several
- different pathways simultaneously.
- PMCID: PMC4479826
- PMID: 26109079
- [9] Prevent Heart Attack and Stroke with Potent Enzyme that Dissolves Deadly Blood Clots in Hours. Health Sciences Institute, March 2002.
- [10] Maruyama M, Sumi H. Effect of Natto Diet on Blood Pressure. JTTAS, 1995
- [11] Sumi H, Hamada H, Nakanishi K, Hiratani H. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84(3):139-43.
- [12] Sumi H, Hamada H, Mihara H. A novel strong fibrinolytic enzyme (nattokinase) in the vegetable cheese "natto." International Journal of Fibronolysis and Thrombolysis.
- [13] Abstracts of the ninth international congress on fibrinolysis, Amsterdam, 1988, Vol.2, Sup.1:67. 5.
- [15] Sumi H. Healthy Microbe "Bacillus natto". Japan Bio Science Laboratory Co. Ltd.
- [16] Sumi H. Structure and Fibronolytic Properties of Nattokinase.
- [17] Chang YY, Liu JS, Lai SL, Wu HS, Lan MY (2008). "Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds". Intern. Med. 47 (5): 467–9. PMID 18310985.doi:10.2169/internalmedicine.47.0620.
- [18] Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med . 2008;47(5):467-469.
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