Into the Heart

A Protective Role for Genistein in the Vascular System

Genistein a soy-derived phytoestrogen has various biological actions including a weak estrogenic effect and inhibition of tyrosine kinases. Data from animal and in vitro studies suggest a protective role of genistein regarding blood vessels.

Studies demonstrate that genistein has anti-atherogenic effects and inhibits proliferation of vascular endothelial and smooth muscle cells.  Several human intervention studies suggest a beneficial effect on atherosclerosis, markers of cardiovascular risk, vasomotor tone, vascular endothelial function, and systemic arterial compliance.

Genistein also inhibits human platelet aggregation in vitro and decreases TNF-induced monocyte chemoattractant protein-1 secretion in human vascular endothelial cells.

Monocyte chemoattractant protein-1 is associated with early phase monocyte infiltration into the coronary vessels which eventually causes arteriosclerosis (medial thickening and fibrosis) of coronary arteries.

The adhesion of mononuclear cells (monocytes) and their infiltration into the blood vessel wall are  crucial early arteriosclerotic events. Genisteins ability to slow or block this cellular activity helps lessen the development of blockage in coronary arteries during the early stage of coronary artery disease.

Source:
Genistein Acutely Stimulates Nitric Oxide Synthesis in Vascular Endothelial Cells by a Cyclic Adenosine 5'-Monophosphate-Dependent Mechanism. Dongmin Liu, Laurie L. Homan and Joseph S. Dillon
Endocrinology Vol. 145, No. 12 5532-5539
© 2004 by The Endocrine Society

Role of Monocyte Chemoattractant Protein-1 in Cardiovascular Remodeling Induced by Chronic Blockade of Nitric Oxide Synthesis. Masamichi Koyanagi, MD
Circulation. 2000;102:2243.
© 2000 American Heart Association, Inc.

Phytoestrogens Genistein and Red Clover

Dietary isoflavones are considered to be cardioprotective due to their structural similarity to estrogen. Estrogen is believed to have beneficial effects on endothelial (blood vessel lining) function and may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease.

Decreased nitric oxide production and endothelial nitric oxide synthase activity, and increased endothelin-1 concentrations, impaired lipoprotein metabolism and increased circulating inflammatory factors often result from estrogen deficiency. Endothelin-1 constricts/tightens blood vessels. Nitric oxide is a molecule produced by endothelial cells. Nitric oxide regulates blood pressure and blood flow and has anti-atherogenic factors.

Estrogen acts by binding to estrogen receptors alpha and beta. Isoflavones have been shown to bind with greater affinity to estrogen receptor beta. Estrogen receptor beta is expressed more in the vasculture (blood vessels) than estrogen receptor alpha.

Phytoestrogens are plant derived nonsteroidal compounds with structural similarity to estrogen. Phytoestrogens have ligands for the estrogen receptors ERa and ERb. A ligand is an ion, a molecule, or a molecular group that binds to another chemical entity to form a larger complex. Phytoestrogen possess weak estrogen like biological activity. As such, phytoestrogens help reduce some symptoms of diminished estrogen during late menopause.

Genistein and red clover are isoflavone phytoestrogens. However, soy and red clover contain different mixtures of isoflavones. For example, studies indicate the isolated isoflavones from red clover are cardioprotective because they reduce arterial stiffness and total vascular resistance.

Studies indicate that in addition to antioxidant activities, genistein also has anti-carcinogenic, anti-atherogenic and anti-osteoporotic activities. Legumes such as soy beans and chickpeas are the major dietary source of genistein.

Soybean and red clover are members of an isoflavone subgroup that includes daidzein, formononetin (daidzein precursor), genistein, and biochanin (genistein precursor).

Epidemiological studies indicate reduced cardiovascular risk in populations consuming high-isoflavone diets.

Source:
Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1066.
Isoflavones Reduce Arterial Stiffness
A Placebo-Controlled Study in Men and Postmenopausal Women
Helena J. Teede; Barry P. McGrath

The Anti-inflammatory Activity of DHA/EPA: Flaxseed

Omega 3 (DHA/EPA) have natural anti-inflammatory activity because they inhibit the conversion of arachidonic acid to the pro-inflammatory: prostaglandin E2, thromboxane A2 and leukotriene B4, as well as the pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-a) and interleukin 1 alpha.

TNF-a is released by stimulated mast cells. Cells involved in inflammation have receptors for TNF-a and are activated to synthesize more TNF-a, this amplifies the inflammation response.

Omega 3 significantly inhibits the lipoxygenase (LOX-5 pathway) which is responsible for the conversion of arachidonic acid to inflammatory leukotrienes in neutrophils and monocytes. This also supresses phopholipase C-mediated signal transduction which is also involved in inflammatory conditions.

Omega 3 also significantly inhibit the conversion of pro-inflammatory arachidonic acid to the enzyme cyclo-oxygenase COX-2.

In addition to salmon, sardines and mackerel; walnuts and flaxseed also have high levels of omega 3.  Hodgson Mill milled flaxseed provides 2600 mg of omega 3 oils per two tablespoons. Hodgson Mill is available in many foodstores in the baking section. Milled flaxseed can be added to oatmeal, cold cereal etc. Enjoy a tablespoon of milled flaxseed throughout the week to help bock inflammatory mediators.

DHA: Cell Protector & Brain Nourisher

DHA has an important role in the metabolic pathways of the peroxisome. The peroxisome is a single membrane organelle present in nearly all eukaryotic cells (membrane bound cell structures). The peroxisome system is involved in several metabolic processes including the oxidation of long and very long chain fatty acids, of cholesterol synthesis, bile acid synthesis, amino acid metabolism and purine metabolism.

Hydrogen peroxide is a byproduct of fatty acid oxidation. The enzyme catalase is an enzyme that prevents hydrogen peroxide from harming the cell. Catalase is located in the peroxisome. DHA enables the catalase enzyme to protect the cell.

DHA is incorporated into the cell membranes of red blood cells, platelet cells and cells of the brain and retina. DHA is a determinant of membrane fluidity in brain cells, is taken up by the brain in preference to other fatty acids. As a brain nourisher; DHA is an essential component in the maintenance of normal cognition and mood. In addition to coldwater fish, walnuts have high levels of omega 3.