Nattokinase Atherothrombotic Prevention Study

Phase

N/A

Condition

Memory Loss

Mental Disability

Dementia

Treatment

Placebo

Nattokinase

Clinical Study ID

NCT02080520

SDF-01

Ages 55-100
All Genders
Accepts Healthy Volunteers

Study Summary

The potential for nattokinase to "thin" blood and to reduce blood clotting by positive antithrombotic and fibrinolytic effects presents a unique opportunity to safely study such effects on cardiovascular disease and cognition. Unfortunately, such studies of antithrombotic and fibrinolytic pathways of prevention have been limited due to lack of safe compounds and the adverse reactions associated with current agents such as Coumadin. Nattokinase, an over-the-counter supplement used for cardiovascular health, is the most active functional constituent of natto, a fermented soy product. Natto has been consumed primarily by the Japanese for over 1000 years, a population with one of the lowest risks for cardiovascular disease and dementia. Cardiovascular disease and dementia remain the most challenging age-related health risks of the 21st century for Americans necessitating development of further effective preemptive strategies. Whether reducing the propensity for thrombus formation and/or increasing fibrinolytic activity can prevent the progression of atherosclerosis and cognitive decline has not yet been determined.

Using nattokinase under primary prevention conditions, the investigators propose to conduct a randomized, double-blinded, placebo-controlled trial to determine whether decreasing atherothrombotic risk can reduce the progression of subclinical atherosclerosis and cognitive decline. The investigators propose to randomize 240 healthy non-demented women and men to nattokinase supplementation or to placebo for three years. The primary trial endpoints will be measurement of carotid arterial wall thickness and arterial stiffness, early changes of atherosclerosis that can be measured safely by non-invasive imaging techniques. The secondary trial endpoint will be ascertained through change in cognition measured by a neuropsychological battery. In addition, biochemical blood measurements and in vitro studies will be conducted to compare the effects of nattokinase relative to placebo on blood coagulation and thrombus break-down capabilities, blood flow properties, inflammation and inflammatory activation of endothelial cells that line blood vessels.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Age >55 years
Male or postmenopausal female (no uterine bleeding for >6 months)

Exclusion

Exclusion Criteria:

Clinical signs, symptoms, or personal history of cardiovascular disease
Diabetes mellitus or fasting serum glucose >140 mg/dL
Plasma triglyceride levels >500 mg/dL
Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic bloodpressure >110 mmHg)
Uncontrolled tachycardia or irregular heart rates (i.e., atrial fibrillation)
Thyroid disease (untreated)
Renal insufficiency (defined as serum creatinine >2.0 mg/dL)
Life threatening illness with prognosis <5 years
Current use of lipid-lowering medication
Current use of food supplements containing soy, soy protein, isoflavones or otherphytoestrogens
Known sensitivity or allergy to soy or nuts
Regular aspirin or other antiplatelet medication use
Use of anticoagulants
Bleeding diatheses or tendencies

Study Design

Placebo

April 01, 2014

July 31, 2019

Study Description

Objectives and Hypotheses: The goal of the proposed study is to determine under randomized controlled trial (RCT) conditions whether nattokinase supplementation reduces subclinical atherosclerosis progression and cognitive decline in healthy women and men. The investigators' hypotheses are: 1) Compared to placebo, nattokinase supplementation will show less subclinical atherosclerosis progression and cognitive decline in healthy women and men; 2) The reduction in subclinical atherosclerosis progression and cognitive decline with nattokinase supplementation will be correlated; and, 3) The reduction in progression of subclinical atherosclerosis and cognitive decline with nattokinase supplementation will be mediated through hemostatic, fibrinolytic, and hemorheological factors as well as attenuation of inflammation, monocyte activation, vascular endothelium injury, and activation of vascular endothelium by circulating monocytes.

Specific Aims: To conduct a RCT to determine the effect of nattokinase supplementation on the progression of subclinical atherosclerosis (primary trial end point) and cognitive decline (secondary trial end point). Healthy non-demented women and men >55 years old without pre-existing symptomatic CVD and diabetes mellitus will be randomized over a 2-year period to oral nattokinase (2,000 fibrinolysis units) daily versus placebo in this double-blind, placebo-controlled trial; randomized treatment will be 3-years. The following 5 major specific aims will be completed:

To determine the effect of nattokinase supplementation on progression of subclinical carotid artery atherosclerosis determined as the rate of change of the common carotid artery intima-media thickness (CIMT) and arterial stiffness in computer image processed B-mode ultrasonograms.

To determine the effect of nattokinase supplementation on cognitive decline determined with a neuropsychological battery designed to evaluate 7 cognitive domains including: attention, concentration, working memory, executive function; visuospatial/visuoconstructive skills; naming/semantic memory; and verbal and nonverbal episodic memory.

To determine the effect of nattokinase supplementation on cognitive decline according to apolipoprotein (Apo) E4 genotype.

To determine the association of subclinical atherosclerosis progression with cognitive decline.

To determine whether the effects of nattokinase supplementation on subclinical atherosclerosis and cognitive decline are mediated through hemostatic (fibrinogen, factor VIII, platelet activity), fibrinolytic (tPA, PAI-1, D-dimer), hemorheological (plasma and blood viscosity, red blood cell aggregation), and inflammatory (MCP-1, IL-8, TNFα, IL-1β, IL-10, monocyte cell surface markers CD11b/CD11c and VLA-4, and cellular adhesion molecules VCAM-1 and ICAM-1) factors as well as blood pressure.

Connect with a study center

Atherosclerosis Research Unit, University of Southern California
Los Angeles, California 90033
United States
Site Not Available
University of Southern California Atherosclerosis Research Unit
Los Angeles, California 90033
United States
Site Not Available

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