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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®:
✓ 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.
Research Proven Health Benefits of Gamma Oryzanol
1) Reduce cholesterol & triglycerides
Numerous studies have supported the role of gamma oryzanol in reducing total cholesterol, LDL (bad) cholesterol and triglycerides levels, and increasing HDL (good) cholesterol in persons with high cholesterol levels. It might help reduce cholesterol levels by reducing the absorption of cholesterol from foods, increasing conversion of cholesterol to bile acids and excretion of bile acids.
In this clinical trial, 40 females aged 38-62 years old were orally administered a total of 300mg gamma oryzanol daily at 3 separate times for 4 to 8 weeks. For those with hyperlipidemia (total cholesterol ≥ 220 mg/dl, triglycerides ≥ 140 mg/dl, HDL-cholesterol ≤ 45 mg/dl), results showed significantly reduced total cholesterol and triglycerides levels and increased HDL-cholesterol, with no side effects observed. In short, gamma oryzanol improved blood lipid profile and could potentially reduce the risk of cardiovascular diseases.
2) Protect against oxidation of blood lipids
Gamma oryzanol is one of the chain-breaking antioxidants. Both sterol and phenolic hydroxyl groups in the gamma oryzanol may be responsible for its antioxidant function. An in vitro study found that gamma oryzanol was more than 4 times as effective as Vitamin E in preventing tissue oxidation. The cholesterol-lowering property of gamma oryzanol may be attributed to its antioxidant function against cholesterol oxidation. Subjects with high blood lipids were orally administered gamma oryzanol for 12 weeks. Results showed gamma oryzanol significantly reduced lipid peroxide levels in the blood serum after 8 weeks and this effect was sustained for another 2 weeks after the administration has stopped.
3) Support healthy blood vessels
Fatty streaks are the first visible sign of atherosclerosis (build-up of fatty deposits) in the arteries. They consist of cholesterol, white blood cells and other cellular matter in the arterial wall. These lesions could occur in the aorta and other arteries of most people by age 20. Over time, fatty streaks can evolve into atherosclerotic plaques, which can restrict blood flow.
In this test, two groups of subjects were fed chow-based diets containing 0.05% cholesterol and 10% coconut oil (control) and the control diet plus 0.5% gamma oryzanol respectively. Compared to the control group, subjects treated with gamma oryzanol showed reduced total cholesterol by 44%, non-HDL-cholesterol by 57% and triglyceride by 46%. In addition, the fatty streak formation in the aorta was significantly reduced 67% (p < 0.01) in subjects treated with gamma oryzanol. In conclusion, the cholesterol-lowering activity of gamma oryzanol was associated with significant reductions in aortic fatty streak formation (Lipids. 32(3): 303-309 (1997)).
4) Maintain healthy glucose levels
In this test, diabetic subjects were administered 50 mg/kg of gamma oryzanol daily. Results showed single-dose and multiple-dose administration remarkably reduced the blood glucose levels of diabetic subjects. In addition, oxidative stress produced by diabetes was found to be significantly reduced by gamma oryzanol, as evident from a significant decrease in the extent of lipid peroxidation (LPO) and increased levels of enzymatic antioxidants, such as superoxide dismutase (SOD) and reduced glutathione (GSH) in the liver. These findings suggest that gamma oryzanol has the potential to effectively reduce blood glucose levels and reduce the oxidative stress induced by diabetes.
5) Suppress harmful clot formation
Harmful blood clots are formed when platelets accumulate and clump together, this can cause blockage in the blood vessels and if not rectified, can lead to a heart attack or stroke. In this test, subjects were administered gamma oryzanol in a 1% cholesterol diet (HCD) or control diet. Gamma oryzanol fed along with cholesterol diet (HCD) significantly suppressed platelet aggregation induced by ADP (Adenosine Diphosphate) and totally suppressed aggregation induced by collagen. On the other hand, gamma oryzanol with the control diet did not change platelet aggregation induced by ADP and collagen.
6) Improve metabolic health
Metabolic refers to the whole range of biochemical processes involved in the normal functioning of the body. Metabolic syndrome refers to a group of risk factors that increase the risk of cardiovascular disease, stroke, diabetes and diseases linked to fatty build-ups in artery wall. This severe health condition affects around 23% of adults. The underlying causes of metabolic syndrome include obesity, a sedentary lifestyle, genetic factors and ageing. To target metabolic syndrome, brain dysfunction such as dependence on animal fat should be addressed.
In this test, subjects were fed with excessive animal fat to evoke the endoplasmic reticulum (ER) stress in the brain hypothalamus, inducing great preference for animal fat intake. Results showed that administration of gamma oryzanol decreased ER stress in the hypothalamic area and alleviated animal fat dependence and animal fat-rich diet-induced high blood glucose. In a crossover clinical trial targeting middle-aged patients with metabolic syndrome, the intake of gamma oryzanol-rich fermented beverage also decreased the preference for animal fat-rich diet, improved the imbalanced gut microbiota, chronic constipation and skin conditions. These findings suggest the beneficial effects of gamma oryzanol in supporting optimal metabolic health.
Gamma oryzanol reduced ER stress which help reduce the dependence on animal fat
7) Reduce the risk of fatty liver
Dietary cholesterol intake has been identified as a factor related to the risk and severity of non-alcoholic fatty liver disease (NAFLD). Test subjects were administered a high calorie diet (HCD) or HCD + gamma oryzanol for 13 weeks. Compared to the control (HCD), gamma oryzanol suppressed the increment of liver weight caused by a HCD, suggesting the protective effect of gamma oryzanol against fatty liver.
8) Improve nervous system
i) Dysautonomia:
Dysautonomia is a condition in which the autonomic nervous system does not work properly. The autonomic nervous system controls the body functions such as heart rate, blood pressure, digestion, kidney function and temperature control. Individuals with dysautonomia have difficulty regulating these systems and have to live with abnormal heart rates, unstable blood pressure, dizziness, fainting spells, malnutrition and in serious cases, death. Currently, there is no cure for any form of dysautonomia.
Gamma oryzanol was reported to improve the condition of post-traumatic dysautonomia from head injuries, with no side effects reported at large dosage. In this clinical trial, 31 dysautonomia patients (12 males, 19 females) aged between 14 and 52 years old were orally administered a total of 45 mg gamma oryzanol daily at 3 separate times for 21 days. Results showed that 74% of dysautonomia condition was improved, suggesting the beneficial effects of gamma oryzanol on the nervous system.
ii) Gynaecological autonomic nervous system
Gamma oryzanol is beneficial to middle-aged and menopausal neuropathy, which is a damage or dysfunction of one or more nerves. It commonly results in numbness, tingling sensations, muscle weakness and pain in the hands, feet and other parts of the body. In addition, gamma oryzanol also supports healthy nervous system on women undergoing hysterectomy (a surgery to remove the uterus).
9) Improve menopausal symptoms
A number of clinical studies have proven that Gamma oryzanol is effective in relieving menopausal (climacteric) symptoms. Approximately 67-85% menopausal women and women whose ovaries were surgically removed experienced a significant reduction in menopausal symptoms with treatment of gamma oryzanol (Chem Parm Bull. 30(3): 973-979 (1982), Murray, M. (1996): Encyclopedia of Nutritional Supplements. Prima Publishing, pp. 332-335).
In this clinical trial, 40 females (aged 38 – 62) who were suffering from menopausal symptoms were orally administered a total of 300 mg gamma oryzanol per day at 3 separate times, for 4 to 8 weeks. The severity of menopausal complaints was measured using the Kupperman Index and a questionnaire. Results showed remarkable improvement in 90% of the menopausal symptoms, with no known side effects. A subjective symptom of a climacteric (menopause) disturbance was recovered 85%, suggesting the beneficial effects of gamma oryzanol on menopausal women.
| Terminology: Vasomotor complaints: Examples are night sweats, hot flashes, and flushes Paresthesia: burning or prickling sensation in hands, arms, legs, feet etc. Insomnia: sleep disorder which includes trouble falling and/or staying asleep Melancholia: a feeling of deep sadness Vertigo: a sense of spinning dizziness Arthralgia: joint pain Myalgia: muscle pain Palpitation: feelings of having a fast-beating, fluttering or pounding heart Formication: feeling of insects crawling across or underneath skin |
10) Improve muscle strength
Research showed that as estrogen levels increase during a woman’s menstrual cycle, HDL (good) cholesterol levels increase and LDL (bad) cholesterol levels decrease as well. During menopause, the decrease of blood estrogen levels leads to an increase in blood cholesterol and development of atherosclerosis (hardening of arteries) in menopausal women. This is because cholesterol is not effectively removed from the blood as the number of low-density lipoprotein cholesterol receptors on body cells increased due to the change in estrogen levels. In this study, menopausal women were found to have significantly higher lipid peroxidation and administration of gamma oryzanol significantly reduced lipid peroxidation in the blood serum. These findings suggest the cardioprotective benefits of gamma oryzanol for menopausal woman.
In a double-blind clinical trial, 30 healthy males (aged 18 to 32) was orally administered 600 mg of gamma-oryzanol or placebo (lactose) after 9 weeks of training. The exercise involved was 80% 1-Repetition Maximum (1-RM), for 1 hour and 4 days/week. Their muscle strength (bench press and leg curl) was determined at the commencement and end of the 9-week study. There were significant differences between the muscle strength of the gamma oryzanol and placebo groups. Oral administration of 600 mg/day of gamma oryzanol for 9 weeks significantly improved muscle strength following the resistance training. These findings supported the efficacy of gamma oryzanol in improving sport performance of athletes.
11) Improve gastrointestinal health
Gamma oryzanol has therapeutic potential for numerous gastrointestinal diseases, including gastric ulcers and colon inflammation.
Study 1: In a test, gamma oryzanol was shown to suppress histamine- and tetragastrin-stimulated gastric secretion and experimental ulcers in subjects. The suppressive effect of gamma oryzanol on gastric secretion was proposed to be mediated by the vagus nerve, which plays a role in the action of gastrin, a hormone that stimulates the secretion of gastric acid (Nihon Yakurigaku Zasshi. 74(2):285-295 (1978)).
Study 2: In another test, experimental colitis was induced in subjects by 1% DSS (dextran sulphate sodium) in drinking water for 16 days with or without 50mg/kg/day gamma oryzanol. Gamma oryzanol was found to improve DSS-induced colon inflammation. This improvement was associated with the suppression of myeloperoxidase (MPO) activity (inflammation marker), decreased production of cytokines such IL-1β, TNF-α, and IL-6, and inhibition of COX-2 and NF-κB activity in colitis tissue. In addition, in vitro assay demonstrated that gamma oryzanol has strong antioxidant effects comparable to those of α-tocopherol. These findings suggested the beneficial effects of gamma oryzanol for treatment of gastrointestinal complaints.
12) Support healthy brain function
Brain inflammation has been suggested as an important factor that contributes and aggravates cognitive decline among the elderly. The antioxidant and anti-inflammatory properties of gamma oryzanol has been demonstrated to cross the blood-brain barrier intact and exert beneficial effects on brain function.
Subjects were orally administered 100 mg/kg gamma oryzanol or control daily for 21 days and then exposed to an inflammatory stimulus elicited by lipopolysaccharide (LPS). Results showed that gamma oryzanol improved cognitive performance during the brain inflammatory response. In addition, gamma oryzanol also upregulated antioxidant enzymes, such as heme oxygenase-1 (HO-1) and NADPH-dehydrogenase-quinone-1 (NQO1) in the hippocampus, a region of the brain associated with memory. Furthermore, gamma oryzanol showed a strong anti-inflammatory activity by downregulating inflammatory genes after LPS treatment. These findings suggest that long-term consumption of gamma oryzanol promotes antioxidant and anti-inflammatory responses, which could help reverse cognitive and memory impairments.
Note: This novel object recognition test was used to assess the effect of gamma oryzanol on long-term memory. Subject treated with LPS lost their ability to differentiate the new object from the familiar object, and indiscriminately explored both. On the other hand, mice pre-treated with gamma oryzanol and subsequently injected with LPS were able to distinguish the novel object, spending more time exploring it than the familiar one.
13) Support healthy kidneys
Obesity and metabolic syndrome are known to affect renal filtration, increasing the risk of chronic kidney disease. The antioxidant and anti-inflammatory activities of gamma oryzanol have shown a positive action in the treatment of obesity and metabolic diseases, which would potentially improve obesity-induced kidney injuries.
In this test, subjects were orally administered high sugar-fat diet (HSF) for 20 weeks. When proteinuria (protein in the urine) was detected, HSF subjects were allocated to receive gamma oryzanol or maintain HSF for more than 10 weeks. The effect of gamma oryzanol to recover renal function in obese subjects by HSF diet was evaluated.
Treatment with gamma oryzanol for 10 weeks resulted in improvement of inflammation, increased antioxidant enzyme activities and recovered renal function. These findings suggest that gamma oryzanol is able to modulate inflammation and oxidative stress pathways, improving obesity-induced renal disease.
14) Support fairer skin
Gamma oryzanol has been shown to have a potent and significant inhibitory effect on melanin formation.
In this in vitro study, B16F1 cells (melanin-producing cells) were treated with 3 and 30µM of gamma oryzanol. Gamma oryzanol significantly reduced melanin content in a dose-dependent manner. In addition, gamma oryzanol effectively reduced tyrosinase activity in a dose-dependent manner. Downregulation of tyrosinase activity has been proposed to be responsible for reduced melanin production. By reducing melanin production and tyrosinase activity, gamma oryzanol is effective in lightening skin tone.
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.
Since plaque build-up and blood clots are major contributing factors of blocked arteries, poor circulation and cardiovascular diseases, maintaining healthy blood vessels clear of harmful clots is crucial in lowering these risks and sudden death.
VesseCLEAR EX & VesseCLEAR CX is developed by Japan Bio Science Laboratory, the leader and pioneer in nattokinase. This 100% concentrated nattokinase NSK-SD® is extracted from non-GMO soybeans which were fermented with Bacillus subtilis natto, via a proprietary process (Patents JP3834048, JP3881494) and results in an extract of high purity, bioavailability and stability.
Nattokinase exhibits strong fibrinolytic activity to support fibrin breakdown, promoting healthy blood flow and supporting optimal cardiovascular function.
What differentiates VesseCLEAR EX and VesseCLEAR CX is its 2nd key ingredient. VesseCLEAR EX additionally contains Elastin F and VesseCLEAR CX additionally contains ORYZA GAMMAX® gamma oryzanol.
Elastin F is a low-molecular-weight elastin peptides derived from bonito fish. It is 1000x more flexible than collagen, and helps keep blood vessels supple and flexible.
ORYZA GAMMAX® gamma oryzanol is extracted from non-GMO rice bran oil. This branded gamma oryzanol is research proven to support healthy cholesterol and triglyceride levels.
When taking VesseCLEAR EX & VesseCLEAR CX
Take 2 (brown) Gamma Oryzanol ORYZA GAMMAX® capsules after a meal.
Take 1 (white) Nattokinase NSK-SD® capsule and 1 VesseCLEAR EX capsule before bedtime.
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