Circulatory Function and Vascular Integrity

Supporting vascular integrity to enhance circulatory function

The plant kingdom also offers beneficial botanicals. Garlic, for example, was found in an animal study at the University of Alabama at Birmingham to protect against increased ventricular pressure via the metabolite allicin’s activity on endothelial function and vasoreactivity.⁷⁴ In fact, the endothelium-modulated vasorelaxation may be mediated through the cyclooxygenase (COX) pathway, beyond NO.⁷⁵ Garlic may also modulate the expression of endothelial leukocyte adhesion molecules, preventing monocyte adhesion.⁷⁶

Aged garlic extract (AGE) has also been the subject of study. In a placebo-controlled, crossover pilot study, pretreatment with 4 mL/d of AGE (as Kyolic® AGE, from Wakunaga) for six weeks significantly improved the endothelial dysfunction induced by acute hyperhomocysteinemia in macro- and microvascular systems.⁷⁷ The researchers noted Kyolic AGE may be useful for maintaining or improving blood vessel function and blood pressure and circulation by preventing a decrease in bioavailable NO and endothelium-derived hyperpolarizing factor.

Additional studies support the theory. A randomized, placebo-controlled, crossover design study in which 15 men with CAD took Kyolic AGE (2.4 g/d) for two weeks found a 44 percent increase in FMD.⁷⁸ In a double blind, randomized clinical study, Kyolic AGE (5 mL/d) taken for 13 weeks by normocholesterolemic adults significantly reduced clotting—both clotting rate and amount—induced by a clotting agent.⁷⁹ Another randomized, double blind clinical trial in moderately hypercholesterolemic men found administration of Kyolic AGE (2.4 and 4.8 g/d) reduced blood levels of LDL and total cholesterol by 5 to 7 percent.⁸⁰ Kyolic AGE also reduced platelet aggregation induced by collagen and epinephrine, and inhibited its adhesion to fibrinogen and collagen. Blood pressure was also reduced.

A phytosome complex of Ginkgo biloba extract (as Ginkgoselect® Phytosome®, from Indena) appears to not only have antioxidant effects but work on vascular disorders. Researchers from Ninewells Hospital & Medical School, Dundee, Scotland, investigated the efficacy of the extract in treatment of Raynaud’s phenomenon (RP), a painful condition characterized by digital ischeaemia, which manifests as blanching caused by artery vasospasm.⁸⁵ In their 10 week trial, subjects received active or placebo treatment; those on active treatment saw a significant reduction (56 percent) in frequency and severity of attacks. Animal studies on Ginkgoselect further show it can increase the bioavailability of the ginkgo phenolic antioxidants and help repair ischemia/reperfusion damage.⁸⁶

The Cochrane Database recently updated its review on hawthorn (Crataegus) for chronic heart failure, finding the botanical does have benefits to the cardiovascular system.⁸⁷ Chinese researchers found hawthorn extract contains active compounds that may increase NO bioavailability and increase vasorelaxation in vitro.⁸⁸ Further in vitro work suggests hawthorn can protect endothelial cells from thrombus formation, possibly by impacting NO and calcium ion levels.⁸⁹ Another study in cultured endothelial cells found hawthorn extract was able to inhibit increased synthesis of endothelin-1 and induce endothelium-dependent vasodilation.⁹⁰

Soy isoflavones may also have a beneficial impact on vascular health. A study out of Stanford University, Calif., examined the effects of dietary isoflavones (as Novasoy®, from ADM) on vascular reactivity, lipid levels and inflammatory markers in post-menopausal women (n=40).⁹¹ Six weeks of supplementation with 90 mg/d of isoflavones improved endothelium-independent vasodilation; there was also a trend toward improvement of flow-mediated vasodilation, and endothelium-dependent response.

Danish researchers conducted a randomized, double blind, placebo-controlled, crossover study with 30 postmenopausal women who received cereal bars, with or without soy isoflavones (50 mg/d) for eight weeks, separated by an eight-week washout period.⁹² Isoflavone treatment significantly improved systemic arterial compliance and endothelium-independent vasodilation, while increasing plasma concentrations of NOx.

Similarly, a study from the University of California, Davis, found when healthy postmenopausal women (n=28) consumed soy protein with isoflavones, it improved vasodilatory response.⁹³ And Italian researchers found providing postmenopausal women (n=60) with isoflavone supplements significantly improved endothelium-dependent vasodilation and reduced plasma adhesion molecule levels.⁹⁴

The mechanisms of action are still being elucidated. However, in vitro studies suggest the isoflavones have direct nongenomic effects on eNOS activity in vascular endothelial cells,⁹⁵ activate iNOS and up-regulate production of NO.⁹⁶

Fermented soy beans, known as natto, also work to enhance the cardiovascular system. In the 1980s, Hiroyuki Sumi isolated the active ingredient from natto, an enzyme that he named nattokinase. That enzyme could break up fibrin into smaller pieces, and upregulates the plasminogen activation system (PAS), an enzymatic cascade involved in the control of fibrin degradation, matrix turnover and cell invasion.⁹⁷ Nattokinase decreases blood viscosity without adversely affecting the normal coagulation cascade.⁹⁸

A recent study out of the University of Southern California, Los Angeles, examined the effects of nattokinase on different blood parameters, and found a significant, dose-dependent decrease of platelet aggregation and low-shear viscosity.⁹⁹ Japanese researchers induced endothelial damage in the rat femoral artery to examine the effects of natto supplementation prior to and after injury.¹⁰⁰ While the femoral arteries reopened in both the natto-treated and control animals within eight hours of injury, the natto suppressed IMT associated with endothelial injury, and showed enhanced thrombolysis near the injury site.

A clinical trial coordinated out of G D’Annunzio University, Pescara, Italy, examined the impact of an oral profibrinolytic supplement (as Flite Tabs, a combination of Pycnogenol and nattokinase) on DVT during long-haul flights.¹⁰¹ A group of 204 subjects at high risk of DVT were randomized to receive the supplement or placebo; after flights, there was an increase in edema in control subjects and a decrease in the intervention group. In addition, the supplement reduced thrombotic events in the subjects.

Another compound used to break down proteins in the body is bromelain, an enzyme isolated from pineapple. Research suggests it may inhibit platelet aggregation and thrombosis with fibrinolytic activity.^102,103 In vitro and in vivo work at the Free University of Berlin, Germany, found incubation of platelets with bromelain could prevent thrombin-induced platelet aggregation and reduce platelet adhesion to endothelial cells.¹⁰⁴ In addition, bromelain orally dosed at 60 mg/kg could inhibit thrombus formation in a time-dependent manner.

Another specialty compound, milk-derived tripeptides, appears to have positive effects on endothelial-dependent and -independent vasodilation. Researchers from the University of Helsinki, Finland, evaluated the anti-hypertensive mechanisms and vascular effects of tetrapeptides from milk protein in spontaneously hypertensive rats (SHR).¹⁰⁵ The tetrapeptides from alpha-lactorphin and beta-lactoglobulin improved vascular relaxation, with the former affecting endothelial function and the latter enhancing endothelium-independent relaxation. The Finnish researchers also reported long-term intake of the peptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) in SHR attenuates the development of hypertension by inhibiting angiotension converting enzyme (ACE), a key regulator for the production of the vasoconstricting hormone Angiotensin 2.¹⁰⁶ Further, there is evidence from animal trials that the opioid receptors may be involved in the ability of tetrapeptides to lower diastolic and systolic blood pressure.¹⁰⁷

Formulators have a broad range of ingredients—and marketers a great opportunity—to address vascular health for long-term wellness. By enhancing the strength of the circulatory system, consumers ensure that there will be blood, where and when they need it throughout the body, and functioning with optimal power. 

Editor's Note: References follow on next page.

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