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The following are extracted from published clinical studies, in-house studies, and/or case studies and are for reference purposes only. This does not imply that the product from Lifestream Group Pte Ltd is claimed to replicate the same results produced in the studies. This information is not a substitute for professional medical advice, diagnosis, or treatment. If you have any questions about a medical condition, please consult your physician or other qualified healthcare providers. Any statements or claims made have not been evaluated by the relevant regulatory bodies and are not intended to diagnose, treat, cure, or prevent any disease.
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Research Proven Health Benefits of Nattokinase NSK-SD®:
Did you know?
NSK-SD® is a proprietary, research-supported form of nattokinase that was the first to be introduced to the global market. It is one of the few nattokinase with published human clinical data examining its safety and effectiveness in supporting cardiovascular wellness.
More than 20 clinical studies have investigated NSK-SD® for its role in promoting healthy blood circulation, maintaining normal blood pressure levels, and supporting the body's natural inflammatory response. Importantly, NSK-SD® has been shown not to interfere with the body’s natural blood clotting response to injury, and does not interact with prescription blood-thinning medications.
Due to the complexity of the nattokinase enzyme, not all products marketed as nattokinase contain the same active components. Independent testing using the I-BOX assay has identified that some commercially available nattokinase supplements may contain enzymes of a different profile. As such, the clinical data specific to NSK-SD® cannot be assumed to apply to other generic nattokinase products that have not undergone the same validation.
NSK-SD® is featured in products such as VesseCLEAR EX and VesseCLEAR CX, which are formulated to support cardiovascular health as part of a balanced diet and lifestyle.
A recent review (Rev Cardiovasc Med. 2023 Aug 15;24(8):234) noted that short-term use of low-dose nattokinase may not produce significant changes in blood lipid levels. It also suggested that the potential benefits of nattokinase on cardiovascular health markers could be more pronounced at higher intake levels. These findings highlight the importance of dosage and duration when evaluating the supportive role of nattokinase in maintaining healthy lipid metabolism and cardiovascular wellness.
Studies on ≥ 4000 FU nattokinase
Study 1: In this clinical trial, 1,062 participants were orally administered 10,800 FU/day of nattokinase for 12 months. At this dosage, nattokinase supported favourable changes in lipid parameters and markers associated with circulatory health. Notable improvements were observed in carotid artery intima-media thickness and plaque measurements — with improvement rates ranging from 66.5% to 95.4%. These changes are relevant as the carotid arteries play a key role in supplying blood to the brain and head.
Interestingly, nattokinase at a lower dose of 3,600 FU/day did not produce similar outcomes. The benefits were more pronounced in individuals who smoked, consumed alcohol, had higher BMIs, and those who engaged in regular exercise — suggesting that nattokinase may work synergistically with certain lifestyle factors. Furthermore, combining nattokinase with vitamin K2 (180 μg daily) and aspirin (100 mg daily) appeared to enhance these effects, with no noticeable adverse events reported.
These results suggest that a 10,800 FU/day dosage is safe, well tolerated, and supports cardiovascular health and lipid balance.
(Note: The nattokinase used in the referenced study is not NSK-SD®, and each capsule contained 3,600 FU. While results are not directly transferable, they support the general understanding of nattokinase’s role in cardiovascular maintenance.)
Study 2: In a controlled clinical study, 30 adult participants following a low-cholesterol diet were given either 4,000 FU of nattokinase or a placebo, taken twice daily for 8 weeks. The group receiving nattokinase showed more pronounced improvements in lipid-related parameters, including total and LDL cholesterol levels, compared to the placebo group.
These findings indicate that daily supplementation of 8,000 FU of nattokinase was well tolerated and may help support healthy cholesterol metabolism when combined with a balanced, low-cholesterol diet.
(Note: The nattokinase used in the referenced study is not NSK-SD®. While results are not directly transferable, they support the general understanding of nattokinase’s role in cardiovascular maintenance.)
Study 3: This randomized, placebo-controlled trial involved 265 individuals (median age 65.3 years) with no clinical signs of cardiovascular disease. Participants were assigned to receive either 2,000 FU/day of nattokinase or a placebo over a median duration of 3 years.
Vascular measurements — including carotid artery intima-media thickness (CIMT) and arterial stiffness — were assessed every 6 months using ultrasound, alongside routine monitoring of blood lipid and glucose levels.
After 3 years, there were no statistically significant differences observed between the nattokinase and placebo groups in terms of changes in vascular measurements or metabolic markers.
These findings suggest that, in generally healthy adults at low cardiovascular risk, long-term supplementation with 2,000 FU/day nattokinase may not produce measurable effects on vascular structure or lipid metabolism.
(Note: The nattokinase used in the referenced study is not NSK-SD®. While the results are not directly transferable, they contribute to the broader evidence base regarding nattokinase and cardiovascular health.)
✓ Supportive effect of Nattokinase NSK-SD® on fibrinolytic markers in healthy adults
In a randomized, placebo-controlled clinical trial, 45 healthy adults were given 4,000 FU/day of NSK-SD® nattokinase or placebo once daily for 8 weeks. Fibrinolytic activity was assessed at baseline, week 4, and week 8.
While overall comparisons between the NSK-SD® and placebo groups did not show statistically significant differences across all participants, a subgroup analysis revealed a notable decrease in total PAI-1 levels in the NSK-SD® group after 8 weeks, particularly among individuals with a BMI > 25.
Elevated levels of PAI-1 are commonly studied as markers associated with reduced fibrinolytic capacity. No adverse effects were observed throughout the study, supporting the tolerability and safety of NSK-SD® at the studied dose.
These findings contribute to the growing body of evidence exploring nattokinase’s potential role in supporting fibrinolytic balance, especially for individuals with a higher BMI.
Reference: EC Nutrition 19.11 (2024): 1–8
✓ Effects of Nattokinase NSK-SD® on immune activity in healthy adults
In a randomized, placebo-controlled clinical trial, 10 healthy male adults (average age 30.2) were given a single oral dose of 4,000 FU NSK-SD® nattokinase or placebo. Blood samples were collected 6 hours post-administration and analysed for changes in natural killer (NK) cell activity — an established marker of immune function.
The results showed that the NSK-SD® group experienced an increase in NK cell activity compared to placebo. A rise in body temperature was also observed in the NSK-SD® group, while no significant changes were noted in blood pressure, consistent with the use of the product in healthy individuals.
These findings suggest that a single dose of NSK-SD® may support immune system activity, particularly through the modulation of cellular immune markers.
✓ Effects of Nattokinase NSK-SD® on metabolic and aging-related markers
In a 14-day dietary study using the streptozotocin (STZ)-induced rat model, animals were assigned to one of three regimens: a control diet, a low-dose NSK-SD® diet (NK-L; 0.2 mg NK/g), or a high-dose NSK-SD® diet (NK-H; 0.6 mg NK/g).
Compared to the control group, rats in the high-dose NSK-SD® group (NK-H) exhibited several statistically significant differences:
• Reduced glycogen deposition in renal tubules, with no change in systemic glucose concentrations;
• Marked reduction in circulating advanced glycation end products (AGEs), which are commonly studied in relation to metabolic stress and aging processes;
• Suppressed increase in C-reactive protein (CRP) levels on day 7, suggesting modulation of inflammation-related markers.
The low-dose NSK-SD® group (NK-L) showed no significant differences from the control in these parameters.
These preclinical findings highlight the potential of high-dose NSK-SD® to influence key biological markers related to metabolic balance and oxidative stress.
Disclaimer: Animal model results are for scientific reference only and do not imply human health benefits. Further clinical studies are required to confirm relevance in humans.
✓ Support clear blood vessels
(Balancing clotting system naturally and thus, does not increase bleeding risk)
In a human clinical trial, healthy young men (22.3 ± 0.6 years old) received either a single dose of 2,000 FU nattokinase NSK-SD® or placebo and blood samples were collected and analysed. Results show that nattokinase NSK-SD® enhances fibrinolysis (breaking down of blood clots) and anticoagulation.
✓ Support healthy blood viscosity
In an in vitro study, blood samples from healthy adult individuals were incubated with nattokinase at various doses. Red blood cell (RBC) aggregation was then assessed. The decrease of RBC aggregation suggests its potential benefits on patients having or at risk for cardiovascular diseases.
✓ Improves blood flow
In a human clinical trial, healthy subjects (30s – 40s years old) in the fasting state received 2,000 FU nattokinase NSK-SD® and their blood flow was measured. After a 2-week break, the same subjects received placebo under the same condition. Results showed that nattokinase NSK-SD® increased blood flow, suggesting a possible use of NSK-SD® for healthy circulation.
Blood flow of 3 subjects. The blood flow increases in the order of blue →green →yellow→ orange → red.
Study 2: In another study, the effects of nattokinase NSK-SD® on in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin, a medicine that helps prevent blood clots in arteries. Nattokinase NSK-SD® moderately inhibits platelet aggregation and delays thrombosis following oxidative arterial wall injury, suggesting its beneficial effect on improving blood flow without adverse effects.
Platelet-rich plasma was incubated with nattokinase NSK-SD® and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analysed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregation.
Subjects were orally administered with nattokinase NSK-SD® or aspirin for 1 week, and their major blood vessels in the neck were exposed. Arterial thrombosis (blood clot formation in artery) was induced by applying FeCl3 outside the arterial wall for 10 min, and the blood flow was monitored. Nattokinase delayed the FeCl3-induced arterial blockage in a dose-dependent manner with a high dose (500 mg/kg) of nattokinase fully suppressed the blockage, as achieved with aspirin (30 mg/kg).
✓ Supports healthy blood pressure
Study 1: In a human clinical trial, subjects (20 – 80 years old) with pre-hypertension or stage 1 hypertension and initial untreated systolic blood pressure (SBP) of 130 to 159 mmHg were given 2,000 FU nattokinase NSK-SD® or placebo per day for 8 weeks. Compared to placebo, nattokinase NSK-SD® reduced both systolic and diastolic blood pressure (DBP), suggesting nattokinase may play a critical role in preventing and treating hypertension or high blood pressure.
Study 2: In a human clinical trial, subjects (18 – 85 years) with elevated blood pressure (BP; systolic BP 130 or diastolic BP 90 mmHg) consumed 2,000 FU/day nattokinase NSK-SD® or placebo for 8 weeks and their blood was collected. Consumption of NSK-SD® was associated with a reduction in both systolic and diastolic BP as well as von Willebrand factor (vWF), a cardiovascular risk marker.
✓ Support good cardiovascular health
The American Heart Association justifies C-reactive protein (hs-CRP) as an independent clinical marker for cardiovascular disease (CVD) risk.
In a human clinical trial, subjects with cardiovascular risk factors received one dose of 2,000 FU nattokinase NSK-SD® and their blood was tested. Nattokinase demonstrated the ability to normalise levels of hs-CRP.
✓ Support cardiovascular health along with blood thinners
Study 1: In a human clinical trial, adult patients (average 53.3 years old) with acute ischaemic stroke received 2,000 FU nattokinase NSK-SD® 3 times (total 6,000 FU) a day at 8-hour interval for 7 days. Besides, during these 7 days, 0.4ml low molecular weight heparin (anti-factor Xa, 3,800 IU) 2 times a day by hypodermic injection and low-dose aspirin (150 – 325mg) or clopidogrel were also administered. Heparin (anticoagulant drug), aspirin and clopidogrel (anti-platelet drugs) are blood thinners. All patients were hospitalized within 6 hours of stroke occurrence and the treatment was administered after hospitalization. The overall efficacy data suggests that nattokinase does not lead to progression of underlying stroke. Instead, the combined intake is suggested to enhance fibrinolysis (breaking down of blood clots) and the beneficial effects on stroke patients were observed.
Study 2: In another human clinical trial, patients with cardiovascular disease (CVD) who were taking warfarin potassium tablets at a maintenance dose (1.5 < PT-INR < 3.0) received 2 doses of 1,700 FU nattokinase NSK-SD® after breakfast and dinner per day (3,4000 FU/day) or placebo for 6 months. Some of these patients showed improvement in clinical symptoms (i.e. shortness of breath, cold hands and feet) and biochemical profiles, including activated partial thromboplastin time (aPTT), prothrombin time (PT), D-dimer and plasmin inhibitor complex (PIC). No side effects were observed in all patients taking nattokinase. This study suggests that proper use of nattokinase is safe and effective for CVD patients who are taking warfarin.
✓ Support healthy immunity
In a randomised, double-blind, placebo-controlled clinical trial, 10 healthy males (average age 30.2) were orally administered a single-dose of 4,000 FU nattokinase NSK-SD® or placebo. Their blood samples were then collected at 6 hours following administration for analysis of natural killer (NK) cell activity. NK cells are a type of immune cells necessary in the early immune response to fight against viral infections, especially through clearance of virus-infected cells. Based on the results, administration of single-dose of 4,000 FU nattokinase NSK-SD® enhanced the activity of NK cells. Besides, NSK-SD® group also showed an increase of body temperature. As the subjects are healthy individuals, there was no change in blood pressure.
✓ Effects of NSK-SD® on peripheral skin temperature recovery after cold exposure
In a randomized, placebo-controlled clinical trial, healthy adult men received a single oral dose of either 2,000 FU NSK-SD® nattokinase or placebo. Two hours after administration, participants immersed both hands in 10°C water for one minute to induce temporary cooling.
Following cold-water immersion, the skin temperatures of the middle finger, palm, and back of the right hand decreased in all participants. However, temperature recovery was significantly faster in those who received NSK-SD® compared to the placebo group.
Importantly, acute administration of 2,000 FU NSK-SD® had no observable effect on heart rate, cardiac output, or sympathetic nervous system activity compared with placebo, demonstrating good tolerability.
These findings suggest that NSK-SD® may support healthy circulation and temperature regulation following exposure to cold conditions.
✓ Nattokinase NSK-SD® shown to support vascular health and recovery
In this clinical trial, adults of both sexes aged 18 and above, with various vascular health conditions and no prior exposure to pharmacological treatments such as anticoagulants or antiplatelets, were divided into three groups.
• Group 1 included individuals with venous concerns and received subcutaneous fondaparinux (7.5 mg/day) for 30 days, followed by oral nattokinase NSK-SD® (2,000 FU/day) for another 30 days.
• Group 2 consisted of individuals with superficial vein conditions who received enoxaparin (6,000 IU/day) subcutaneously for 30 days, then NSK-SD® (2,000 FU/day) for 30 days.
• Group 3 involved individuals recovering from venous surgery, who began NSK-SD® (2,000 FU/day) one day post-operation and continued for 30 days.
Across all groups, participants reported improvements in circulatory comfort indicators, and no adverse interactions or safety issues were observed. Notably, during the follow-up period, no new vascular events were recorded.
These findings support the potential of NSK-SD® to contribute to vascular health maintenance and circulatory support.
Research-Proven Health Benefits of Elastin F:
✓ Support healthy & flexible blood vessels
In a human clinical trial, healthy subjects (average age of 45.8) were orally administered 75mg Elastin F daily for 16 weeks and their pulse wave velocity was measured every 4 weeks to determine the ageing and stiffness of blood vessels. Supplementation with Elastin F significantly reduced vascular ageing and improved resilience of blood vessels.
✓ Support clear blood vessels
In an in vitro study, platelet-rich plasma was incubated with elastin peptide from bonito (Elastin F), elastin polypeptide from bonito and elastin peptide from bovine. Elastin F showed the highest inhibitory activity on platelet aggregation. This suggests that Elastin F could reduce formation of harmful clots in blood vessels and lower the risk of cardiovascular diseases.
✓ Support skin health
Study 1: In a double-blind trial, Japanese women in their 30s were orally administered 100mg Elastin F (+ 1000mg collagen + 30mg hyaluronic acid + 100mg chondroitin sulfate) or
placebo (1000mg collagen + 30mg hyaluronic acid + 100mg chondroitin sulfate) daily for 8 weeks. Addition of Elastin F to basic skin-care regimen resulted in significant improvement in skin suppleness, texture and reduction in wrinkles.
Subjective evaluation showed improvements in fine lines, dry face, smoothness and lasting duration of make-up.
Study 2: Fibroblasts are cells within the dermis layer of human skin that produces elastin and collagen. In this study, different concentrations of Elastin F were added to human skin fibroblast culture medium. Elastin F was found to help improve structural integrity and function of skin dermis, which are important for maintaining skin firmness and elasticity.
✓ Support joint health
In a double-blind trial, subjects were given placebo, 75mg Elastin F or 75mg Elastin F + glucosamine daily for 12 weeks and improvements were monitored using Visual Analogue Scale (VAS). Remarkable reduction in knee pain was observed in both Elastin F groups but not the placebo group. This suggests the synergistic effect between Elastin F and glucosamine in reducing knee pain.
Nattokinase NSK-SD® supports healthy aging at the cellular level, or, helps reduce the formation of Advanced Glycation End Products (AGEs)
Patented function: Supports the regulation of Advanced Glycation End Product (AGE) formation (Japanese Patent No. 7804957)
As we age, supporting metabolic balance becomes an important part of overall wellness. Advanced Glycation End Products (AGEs), which are linked to the aging process, are substances that form naturally when sugars interact with proteins or fats in the body. Over time, these substances accumulate and damage cells, which are associated with normal aging processes and may affect cellular function over time. This buildup is associated with natural aging processes and may influence overall metabolic health. such as damage to blood vessels and organs. By reducing the formation of AGEs, it may be possible to slow cellular aging and help maintain normal blood sugar levels and its related health problems.
In this study, streptozotocin (STZ)-induced diabetic rats were maintained on a basic diet as a control, a low-NK (nattokinase) diet (0.2 mg NK/g diet), or a high-NK diet (0.6 mg NK/g diet) for 14 days. NSK-SD as the source of NK. High-dose NK significantly inhibited glycogen deposition in the renal tubules, suggesting a supportive effect on normal physiological function. The AGE (Advanced Glycation End Products) level in the control group with induced diabetes was significantly higher than in the Sham group without diabetes. AGE levels were reduced in a dose-dependent manner in the NK groups, with the high-NK group showing the most significant reduction. Furthermore, compared with the control group, rats treated with the high-NK diet showed a significant suppression of the increase in circulating CRP levels on day 7, suggesting a role in supporting normal immune response. These findings indicate that NK suppresses glycogen deposition in renal tubules in a dose-dependent manner through mechanisms associated with the regulation of AGE formation under elevated glucose conditions in STZ-induced diabetic rats. Since AGEs contribute to aging and diabetic complications, NK’s inhibition of AGE formation highlights its potential role as an ingredient that supports general health and healthy aging.
Common Remedies for Circulatory Health in the Market
1) Blood Thinners (Medications)
Blood thinners are prescribed medicines that prevent blood clots from forming. They also keep existing blood clots from getting larger. There are 2 main types of blood thinners –
anticoagulants and antiplatelet drugs.
• Anticoagulants slows down the body’s process of making clots.
• Antiplatelet drugs prevents platelets from clumping together to form a clot.
However, blood thinners may cause side effects in some people. Serious bleeding is the most common reaction - heavy periods, bleeding gums, prolonged
bleeding from a cut, etc. Other possible side effects include dizziness, muscle weakness, hair loss or rashes. Besides, the presence of blood thinners in body system can increase the risk of internal bleeding after an injury, even if external bleeding did not occur.
2) Supplements
Although there are many types of Nattokinase available in the market, did you know that nattokinase activity may decrease when mixed with certain foods/ingredients such as red yeast rice (Monascus ruber-fermented rice), black vinegar, apple vinegar and vitamin C. Please note that the efficacy of nattokinase NSK-SD® will not be affected by the presence of Elastin F in VesseCLEAR EX.
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Did you know that natto is also linked to longevity? (Biosci Biotechnol Biochem 77(2): 392-394 (2013)). |
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The presence of lipofuscin in the skin is associated with the appearance of pigmentation commonly known as liver spots.
Designed for those with greater circulatory needs or metabolic health concerns.
NSK-SD® is the only nattokinase with published clinical data.
Other nattokinase brands can’t borrow NSK-SD®’s studies to make their own claims.
Ultimate VesseCLEAR EX is formulated with Nattokinase NSK-SD® which is free of vitamin k2. This allows those on blood-thinning medication to experience the full benefits of nattokinase.
Not all nattokinase is free from vitamin K2, so always check the label.
