Into the Heart

Red Wine Improves Insulin Sensitivity

Extensive studies have shown that red wine consumption is associated with less cardiovascular mortality in the general population and diabetic individuals.  The ability of red wine to improve insulin sensitivity is a key cardioprotective mechanism.

The phrase "insulin sensitivity" refers to the ability of cells to accept glucose. Insulin is a transporter and regulator of glucose. After glucose is taken up by cells, insulin has completed its task. Circulating insulin levels are then lowered. The glucose is used by the cell for energy.

If cells are not receptive (sensitive) to insulin . . . cells will lack (glucose)energy/fuel. Circulating insulin levels will remain high and too much glucose will say in the bloodstream, which contributes to high cholesterol and triglycerides. Increased insulin also causes stored body fat.

A 2004 study conducted in Italy explored the relationship between insulin sensitivity and red wine consumption. The study analyzed two groups of individuals with type 2 diabetes. One group consumed red wine for two weeks. The other group did not consume red wine.  The study group with type 2 diabetes, that consumed red wine, improved insulin mediated whole body glucose disposal by 43%.  Insulin mediated whole body glucose disposal did not change in the non wine drinking group.

Two weeks of red wine consumption markedly attenuated (lessened) insulin resistance in type 2 diabetics.

Source:
Red wine consumption improves insulin resistance but not endothelial function in type 2 diabetic patients
NAPOLI Raffaele; COZZOLINO Domenico ; GUARDASOLE Vincenzo MDs
Metabolism, Clinical and Experimental   
2005, vol. 54, no3, pp. 306-313

Preventing Clogged Arteries

Thrombosis is the formation or presence of a blood clot in a blood vessel (vein or artery).  The clot itself is termed a thrombus and is composed of insoluble fibrin, deposited platelets, accumulating white blood cells and entrapped red blood cells.

A thrombus (blood clot) may stay attached to the artery wall creating blockage (occlusion).
An embolus is a traveling blood clot. The blockage that is causes is called an embolism.

A micro-embolism occurs when small platelet aggregates break off from the thrombus and flow downstream, where they can occlude tiny arterioles and capillaries (micro-circulation) that deliver oxygen and nutrients to the heart and brain.

The interaction of platelets with collagen in the blood vessel wall is an originating step in platelet aggregation (build-up) leading to thrombosis.  Activated platelets release thromboxanes A2 from arachidonic acid in the phospholipids of the platelet membrane.

Platelets, platelet products, and clotting factors have causal roles in the occurrence of virtually all occlusive vascular events including heart attack and stroke.

Platelet aggregation is inhibited by cyclic AMP and by acetyl-salicylic acid (aspirin).

Incorporating eicosapentaenoic acid (EPA) in the diet reduces the frequency of thrombosis by reduction of thromboxane A2 production. (EPA) is provided in omega 3 foods such as fish oils, milled/ground flaxseed and walnuts.

Resveratrol, the polyphenolic compounds in red wine significantly inhibit platelet aggregation.

Four ounces of lowfat yogurt, sprinkled with walnuts and a tablespoon of ground flaxseed is a heart healthy breakfast. Broiled salmon with rosemary & lemon is a heart healthy dinner option. Several small servings of red wine during the week help nurtures cardiovascular health by preventing platelet aggregation .

Sources:
Alcohol, Wine and Platelet Function
JEAN-CLAUDE RUF
Biol Res 37: 209-215, 2004

The Red Wine Phenolics Trans-resveratrol and Quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease.
Pace-Asciak CR, Hahn S, Diamandis EP, Soleas G and Goldberg DM
Clin Chim Acta  235: 207-219 (1995)

Dietary fish oils containing eicosapentaenoic acid and the prevention of atherosclerosis and thrombosis.
B J Holub
Canadian Medical Assoc Journal. 1988 September 1; 139(5): 377–381.

Lowering C-Reactive Protein Levels: A Predictor of Coronary Artery Disease

Information about the inflammatory state of an individual is clinically relevant since factors that determine inflammation can be modified.

C-reactive protein (CRP) is an acute phase protein produced by the liver in response to tissue injury, inflammation, or infection. The physiological role of C-reactive protein is to direct inflammatory remnants to phagocytic cells of the lymphatic system for elimination.

Coronary Artery Disease: atherosclerosis is the process in which fatty deposits build up in the inner lining of arteries. It is considered to be a low-grade inflammatory disease.

Studies have shown that plasma levels of CRP are a strong independent predictor of endothelial dysfunction, future myocardial dysfunction, stroke, and peripheral artery disease among individuals without known cardiovascular disease.

Testing CRP levels in the blood is an additional way to assess cardiovascular disease risk.  A test called a highly sensitivity C-reactive protein (hs-CRP) assay can help determine cardiovascular disease risk.

C-Reactive Protein and Estrogen Replacement
Hormone replacement therapy for menopausal and postmenopausal women effects CRP levels. The effect of estrogen replacement on CRP is dependent on the route of administration. Studies show that transdermal estrogen replacement does not effect CRP, where oral estrogen replacement therapy increases CRP.

Transdermal estrogen replacement is not subject to first pass metabolism by the liver, this allows for  lower doses and exposes tissues to lower drug levels. Lower exposure in the liver impacts protein and lipid synthesis.

As such, in postmenopausal women, oral but not transdermal ET increased CRP by a first-pass hepatic effect. An increase in CRP levels is accompanied by a reduction in IGF-1, an anti-inflammatory growth factor.

Red Wine benefits C-Reactive Protein
Polyphenol rich red wine has pronounced anti-inflammatory effects. In particular, the resveratrol content in red wine helps inhibit tumor necrosis factor a (TNF-a) induced NF-KB activation and inflammatory gene expression and attenuates (lessens) monocyte adhesiveness to human coronary arterial endothelial cells.

At nutritionally relevant concentrations, red wine reduces the susceptibility of LDL cholesterol to (oxidation) lipid peroxidation. Oxidized LDL cholesterol is the prominent component of atheromas (fatty deposits in the arteries). Inhibiting the oxidation of LDL cholesterol blocks the initiation of a cascade of inflammatory mediators in the arterial wall causing a reduction in atherosclerotic processes. The polyphenolic compounds in red wine have antioxidant and anti-inflammatory effects which maintain lower C Reactive Protein levels and lowers the risk of cardiovascular disease.

Sources:
High Sensitivity C Reactive Protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease.
Circulation, 2001 ;103: 1813-1818.

Resveratrol attenuates TNFa induced activation of coronary arterial endothelial cells:
Role of NF-KB inibition
Anna Csiszar, Kira Smith, Nazar Labinsky
Am J Physiology Heart Circulatory Physiology 291: 1694-1699, 2006

Differential effects of oral versus transdermal estrogen replacement therapy
on C-reactive protein in postmenopausal women
Wanpen Vongpatanasin, MD, FACC Meryem Tuncel, MD, Zhongyun Wang, MD
J Am Coll Cardiol, 2003; 41:1358-1363,

Red Wine Decreases the Initiation of Coronary Artery Disease

Inflammatory mediators have a significant role in the initiation, progression, and eventual rupture of atherosclerotic plaques.

The endothelium is a thin protective layer of cells that regulate the structure and function of the arterial wall. The adherence of monocytes to vascular endothelial cells and their migration into the the subintimal space are essential to the initiation of coronary artery disease.

Cellular adhesion molecules orchestrate the process of leukocyte rolling, adhesion and transmigration into the intima layer of the artery. Monocyte Chemoattractant Protein-1 directs monocytes into the arterial intima. Once within the intima layer of the artery monocytes differentiate into macrophages where they internalize/ingest modified lipoproteins such as oxidized LDL cholesterol. The oxidized LDL cholesterol generates a cascade of cellular events that eventually lead to plaque formation, hardening of the arteries and acute coronary events.

There are three major classes of cellular adhesion molecules: selectins, integrins and immunoglobins.
Inhibiting the direction, & adhesion of these cellular mechanism helps block the initiation of coronary artery disease.

A recent study conducted by The University of Barcelona, Spain concluded that medium level polyphenol rich red wine like Spanish sparkling wine decreased circulating biomarkers of coronary artery disease and cellular adhesion molecules such as vascular cell and intercellular adhesion molecules, E and P selectins, and monocyte chemoattractant protein-1 and CD40L. 

Previous studies have demonstrated red wines with higher levels of polyphenols such as Pinot Noir, Red Bordeaux provide cardiovascular protective effects by helping prevent the oxidation (decay) of LDL cholesterol, inhibition of platelet aggregation, and induction of nitric oxide release: vasorelaxation. 

The Barcelona study concluded that even red wines with medium level polyphenol content have a significant role in preventing the initiation and progression of coronary artery disease.

As such, light textured thin Itallian reds wine such as Bardolino or Red Lambrusco and a charming Red Beaujolais from the French country side can also protect arterial integrity and lower the risk of coronary artery disease.  Four ounces of red wine; four servings per week affords cardioprotective benefits.

Sources:
Inflammatory Markers of Atherosclerosis Are Decreased after Moderate Consumption of Cava (Sparkling Wine) in Men with Low Cardiovascular Risk
Mónica Vázquez-Agell and  Emilio Sacanella MD’s,
J. Nutr. 137:2279-2284, October 2007

Activity in Vitro of Resveratrol on Granulocyte and Monocyte Adhesion to Endothelium.
Maria E Ferrero, Albert Bertelli MD's
Am J Clin Nutr 1998;68:1204-14.

Blocking Build Up in the Artery: Intimal Proliferation

The intimal layer of the artery lies just below the endothelium. Smooth muscle cells are responsible for maintaining vascular tone and normally lie in the medial layer of the artery.  During the atherosclerosis process smooth muscle cells from the media of the artery (along with foam cells) migrate and proliferate in the intimal layer of the artery.  Upon migration smooth muscle cells reproduce themselves (divide) and make (synthesize) connective tissue. Macrophages stimulate the migration, proliferation of smooth muscle cells and synthesis of connective tissue (collagen).

The process of smooth muscle cell migration, division and synthesis is referred to as intimal proliferation (buildup) and causes thickening and narrowing of the intima. Smooth muscle cells contribute to a substantial bulk of the atherosclerosis lesion which may protrude several millimeters above the surface of the intima.  As the fatty streak and fibrous plaque enlarge and bulge into the lumen, the sub endothelium becomes exposed to the blood at sites of endothelial retraction or tear, as a result platelets aggregate and mural thrombi form.

The growth of smooth muscle cells depends upon factors derived from the endothelium or platelets. Prostaglandins, thromboxanes, leukotrienes, angiotensin II, catecholamines and cytokines such as TNFa, interleukin and interferon also have a role in the proliferation and/or migration of smooth muscle cells.

Protein Kinase C (PKC) is involved in smooth muscle cell proliferation. Vitamin E, alpha tocopherol inhibits PKC activity by attenuating the generation of membrane derived diacylglycerol: a lipid that facilitates PKC translocation thus increasing its activity.

Mitogen activated protein kinase (MAPK) is also involved in smooth muscle proliferation. Both alpha tocopherol and gamma tocopherol  (vitamin E)  help inhibit MAPK activity.

The isoflavone compound genistein (soybeans/chickpeas) is a broad spectrum protein tyrosine kinase inhibitor.

As such, soy muffins with sunflower seeds (vitamin E) enhance arterial health.

Sources:
Genistein, A Protein Tyrosine Kinase Inhibitor inhibits Thrombane A2
American Society for Pharmacology and Experimental Therapeutics
Volume 39, Issue 4, pp. 475-480,

Genistein Acutely Stimulates Nitric Oxide Synthesis in Vascular Endothelial Cells by a Cyclic Adenosine 5 Monophasphate Dependent Mechanism
Endrocrinology Vol. 145, No 12

Vitamin E Prevents LDL Cholesterol Damage

Vitamin E prevents cell membrane damage by inhibiting peroxidation of membrane phospholipids and disrupting free radical chain reactions induced by formation of lipid peroxides. Peroxidation is the process by which fatty acids get oxidized (rancid).

The oxidation of LDL cholesterol is considered to be a trigger  for a number of cellular events which lead to the formation of atherosclerotic plaque. This includes the uptake of oxidized LDL- by monocytes which leads to foam cell formation, endothelial cell damage and stimulation of cytokine and growth factor release from cells in the artery wall. Vitamin E protects LDL cholesterol from oxidation, thereby limiting the initiation of plaque formation in the arteries.

The Daily Reference Intake of vitamin E for individuals over age fifty is 15 mg.
Vitamin E is found only in foods of plant origin and predominantly in plant oils. 
One fourth a cup of sunflower seeds, contains 17.0 mg vitamin E, one tablespoon of sunflower oil contains 7.0 mg, two tablespoons of peanut butter contains 3.3 mg, and two tablespoons of wheat germ contains 2.6 mg of vitamin E.

Vitamin E is a fat-soluble vitamin; its bioavailability depends on fat intake for stimulation of bile acids required for micelle formation. As such, sliced red grapes with a dallop of sour cream (fat content) and a tablespoon of sunflower seeds is a healthful snack.

Vitamin E occurs in food as tocopherols or tocotrienols. Alpha-tocopherol has the highest bioactivity. Vitamin E occurs naturally as d-alpha-tocopherol. The synthetic version is the dl-isomer has 25% less bioactivity than the d-isomer.  A vitamin supplement that lists "dl"-alpha-tocopherol in the ingredient is less expensive and less potent.

Vitamin E along with selenium, copper, and manganese are integral components of the cellular antioxidant defense system.

Red Wine . . . Supple Arteries

Studies have shown that healthy people with the stiffest blood vessels were three times more apt to develop high blood pressure over a five year span than those with supple, pliable vessels.

In a large scale study involving 3,075 healthy older people, those who had the highest pulse wave velocity (PWV) a measure of arterial stiffness, were three times more likely to die of cardiovascular disease than those who had the lowest PWV.

The well being of your arteries depends on a healthy endothelium, the inner lining of your blood vessels. Endothelial cells control almost every activity that occurs in the blood vessels.

Healthy endothelial cells produce nitric oxide, an important signaling molecule that helps keep arteries supple. When nitric oxide enters a cell it stimulates a biochemical process that relaxes and dilates blood vessels. Nitric oxide also helps keep arteries flowing freely by preventing platelets and white blood cells from sticking to the blood vessel wall.

Smoking 1 cigarette causes a significant impairment in endothelial function.
Red wine's antioxidant substances enhance production of nitric oxide.

"People who maintain a healthy endothelium as they get older and those who make an effort to do things that promote the repair of injured endothelium can reduce the risk of heart attacks and strokes caused by atherosclerosis or hypertension" (Edward Lakatta MD, National Institute on Aging USA).

Sources:
Aging Hearts & Arteries
National Institutes of Health USA 2005

J Am Coll Cardiology.
Red wine increases the expression of human endothelial nitric oxide synthase:
a mechanism that may contribute to its beneficial cardiovascular effects.
Wallerath T, Poleo D, Li H, Förstermann U. 2003 Feb 5;41(3):479-81.

Red Wine Lessens Arterial Build-up

The intima layer of the artery lies just below the endothelium.  Smooth muscle cells normally lie in the media layer of the artery.  Smooth muscle cells are responsible for maintaining vascular tone.  During the atherosclerosis process smooth muscle cells along with macrophages (foam cells) proliferate in the intima layer of the artery.

The process of migration, division and synthesis is referred to as intimal proliferation (buildup) and causes thickening of the intima.  Smooth muscle cells from the media move (migrate) into the intima, these smooth muscle cells reproduce themselves (divide) and make (synthesize) connective tissue. Smooth muscle cells contribute to a substantial bulk of the atherosclerosis lesion which may protrude several millimeters above the surface of the intima. As such, the artery becomes narrow, which reduces blood flow to tissues. A narrow coronary artery will reduce blood flow (oxygen & nutrients) to the myocardium: the heart muscle.

The proliferation of vascular smooth muscle cells has a significant role in the progression of atherosclerosis. Resveratrol has been found to inhibit the proliferation of vascular smooth muscle cells in culture.* Resveratrol is a polyphenolic compound found in the skin of red grapes.  Red wine is a rich source of resveratrol.

*Resveratrol Source:
Linus Pauling Institute
Oregon State University

Resveratrol, Red Wine the Vascular Benefit

Resveratrol is an antioxidant compound present in red grapes, red wine and peanuts.

Oxidized (rancid) LDL cholesterol is considered to be a powerful initiating mechanism of atherogenesis: the formation of fatty deposits in the arteries. Red wine phenolics such as resveratrol protects low density lipoproteins (LDL-C) against oxidation.

In addition, the cardioprotective effects of resveratrol are correlated with superior anti-platelet aggregation activity, antioxidant activity, up-regulation of nitric oxide synthase, reduction of smooth muscle cell proliferation and protection against endothelial dysfunction.

Resveratrol helps inhibit the synthesis of thromboxane B2, which induces vasoconstriction (tightening of the arteries). Tight coronary arteries reduce blood flow to the heart and place strain on the heart.

Red Wine and HDL the good cholesterol

High density lipoproteins (HDL cholesterol) transports cholesterol away from the arteries and is refered to as good cholesterol.  One 3 to 4 oz small  glass of red wine per day helps to increase levels of high density lipoproteins. This HDL cholesterol helps to remove some of the low density lipoproteins (LDL cholesterol) from the circulation, which lessens the amount of material available for fatty plaque formation.