Circulatory Function and Vascular Integrity

Supporting vascular integrity to enhance circulatory function

Studies link coenzyme Q10 (CoQ10) to improved vascular health. Italian researchers noted CoQ10 is best known for its role in mitochondrial function; however, it also appears to help reduce cardiac contractility and endothelial dysfunction, while improving FMD.²⁹ A study in patients with coronary artery disease (CAD) found supplementation with CoQ10 (300 mg/d) could improve endothelium-dependent vasodilation, possibly through its antioxidant effects, protecting NO from oxidation.³⁰ Further work by the Italian team also demonstrated adding CoQ10 (300 mg/d) to patients with chronic heart failure (CHF) could improve functional capacity, endothelial function and ventricular contractility.³¹

Another basic nutrient with a critical role to play in the circulatory system is the amino acid L-arginine. Reviewers from Brigham & Women’s Hospital, Boston, noted L-arginine is required by eNOS to produce NO, and administration of L-arginine in several animal and clinical trials has shown its ability to improve endothelial function.³² One such trial was conducted at Baylor College of Medicine, Houston, in which deep vein thrombosis (DVT) was created in animals, which were then randomized to have the thrombus removed mechanically with or without intravenous L-arginine.³³ Adding L-arginine to the treatment decreased platelet deposition and increased endothelium-dependent relaxation. Another study, out of the University of Torino, involved type 2 diabetics (n=24) who received L-arginine plus N-acetylcysteine (NAC) for six months; intervention helped reduce arterial blood pressure and IMT, and increased NO bioavailability.³⁴

Potent Plants

The plant kingdom supplies a cornucopia of options, packed with phytochemicals. One of the best known for its impact on the cardiovascular system is the grape. Studies have looked at the benefits of grapes via red wine, grape seed extract, and even delved into its specialty compound resveratrol. English researchers noted in a review that regular consumption of red wine is linked to a reduced risk of heart disease, and it is likely the polyphenols supply vasoactive support.³⁵ In vitro, red wine and grape seed extract inhibits platelet aggregation and activation by stimulating certain cell adhesion molecules, an activity attributed to its polyphenol content.^36,37 Researchers from the University of South Florida, Tampa, also found grape seed extract has endothelium-dependent relaxing activity, related to NO release.³⁸

Studies out of the University of California, Davis, have sought to examine the effects of a specific grape seed extract on endothelial function and arterial pressure. In an in vitro study, researchers applied GSE (as MegaNatural BP®, from Polyphenolics) to rabbit aortic rings, and found the extract could produce a dose-dependent relaxation when the rings were contacted with noradrenaline.³⁹ Relaxation was inhibited by removal of the endothelium, underscoring the role of eNOS in the response; the extract was also found to activate the P13K/Akt signally pathway, resulting in phosphorylation of eNOS.

Clinical work by the team supports the efficacy of MegaNatural BP. In a 2006 study, 24 adults diagnosed with metabolic syndrome received a placebo, or 150 mg/d or 300 mg/d of the patented GSE.⁴⁰ After one month, the participants taking GSE had reductions in systolic and diastolic blood pressure. A two-month follow-up study involved pre-hypertensive subjects who received 300 mg/d of MegaNatural BP or placebo. Those on the intervention had a significant decrease in systolic and diastolic blood pressure, which the researchers attributed to the vasodilation effects of the GSE polyphenols.

Another branded standardized grape seed extract complexed with soy phosphatidylcholine (as Leucoselect™ Phytosome®, from Indena) has been investigated for its impact on arterial health. One study on the extract found it improved the antioxidant capacity of plasma in animals and in humans.⁴¹ Another Italian double blind, randomized, crossover study investigated the impact of Leucoselect (150 mg/d) or placebo in healthy male heavy smokers (n=24).⁴² Supplementation significantly improved oxidative indices and plasma antioxidant defense.

As mentioned earlier, the compound resveratrol, a polyphenolic compound found in grapes, peanuts and some berries, has been considered one of the active polyphenols responsible for the benefits of grape seed extract. French researchers report among different fractions of grape seed extract, the one richest in trans-resveratrol was the most active in relaxing pulmonary arteries, acting directly on smooth muscle, in an in vitro study.⁴³ A study in Taiwan found resveratrol, at low concentrations, could enhance the inhibitory activity of prostaglandins on platelet aggregation.⁴⁴ Researchers from the University of Waterloo, Ontario, examined the impact of resveratrol (low or high intake) on vasomotor function of rat aorta.⁴⁵ Chronic consumption of resveratrol significantly improved endothelium-dependent vasodilation in spontaneously hypertensive, but not normotensive, rats; the researchers attributed the activity to improved NO bioavailability.

Another beneficial beverage for vascular health is tea. A review from the University of Western Australia, Perth, noted tea is one of the major contributors to flavonoid intake in most populations, and its flavonoids possess vasodilator activity, working to improve endothelial function.⁴⁶ Both black and green tea appear to contribute beneficial flavonoids that enhance vascular health.⁴⁷ For example, Iranian researchers examined the impact of consuming 0.5 L black tea on endothelial function in renal transplant recipients.⁴⁸ Black tea consumption improved endothelium-dependent arterial vasodilation as well as brachial arterial diameter and FMD.

However, more research has focused on green tea and, specifically, the catechin epigallocatechin gallate (EGCG). Researchers from the National Center for Complementary and Alternative Medicine (NCCAM), NIH, Bethesda, Md., reported on in vitro research showing EGCG has endothelial-dependent vasodilator actions that are mediated by intracellular signaling pathways that activate eNOS.⁴⁹ Further, Korean researchers report EGCG has dose-dependent anti-thrombotic activities, primarily by inhibiting platelet aggregation rather than impacting coagulation.⁵⁰ And a clinical trial out of the Boston University School of Medicine found acute supplementation with EGCG (300 mg) in patients with coronary artery disease (CAD; n=42) significantly improved brachial artery FMD and endothelial function.⁵¹

Green tea also has an inhibitory effect on iNOS expression in a concentration-dependent manner, according to in vitro work by Italian researchers in two human epithelial cell lines.⁵² It also had auxiliary anti-inflammatory effects in that trial. A specialty green tea extract (Greenselect®, from Indena) specifically appears to protect cardiac myocytes from cell death after ischemia, which enhanced the recovery of ventricular function and hemodynamic recovery.⁵³

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