Jacob said:
Just did a search..and it seems you've tried it...?
Yes.. still have a lot.. barely using it.. it is really hardcore stuff.. hearbeats.. dark circles... the problem is internally.. I am on minoxidil and Miconazole Nitrate 2%topically for now, still looking for a cheap 4% Mico alternative for better results...I am taking this internally also with a lot of other antioxidants and anti inflammatory.
http://www.iherb.com/Metabolic-Maintena ... 38360?at=0
L-methylfolate is the main ingredient in MetanX. It reverses Endothelial dysfunction. way more mg than Metanx also.
Diabetes Metab Res Rev. 2006 Nov-Dec;22(6):423-36.
Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases.
Cersosimo E, DeFronzo RA.
Source
Division of Diabetes, Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Eugenio.Cersosimo@uhs-sa.com
Abstract
Cardiovascular disease affects approximately 60% of the adult population over the age of 65 and represents the number one cause of death in the United States. Coronary atherosclerosis is responsible for the vast majority of the cardiovascular events, and a number of cardiovascular risk factors have been identified. In recent years, it has become clear that insulin resistance and endothelial dysfunction play a central role in the pathogenesis of atherosclerosis. Much evidence supports the presence of insulin resistance as the fundamental pathophysiologic disturbance responsible for the cluster of metabolic and cardiovascular disorders, known collectively as the metabolic syndrome. Endothelial dysfunction is an important component of the metabolic or insulin resistance syndrome and this is demonstrated by inadequate vasodilation and/or paradoxical vasoconstriction in coronary and peripheral arteries in response to stimuli that release nitric oxide (NO). Deficiency of endothelial-derived NO is believed to be the primary defect that links insulin resistance and endothelial dysfunction. NO deficiency results from decreased synthesis and/or release, in combination with exaggerated consumption in tissues by high levels of reactive oxygen (ROS) and nitrogen (RNS) species, which are produced by cellular disturbances in glucose and lipid metabolism. Endothelial dysfunction contributes to impaired insulin action, by altering the transcapillary passage of insulin to target tissues. Reduced expansion of the capillary network, with attenuation of microcirculatory blood flow to metabolically active tissues, contributes to the impairment of insulin-stimulated glucose and lipid metabolism. This establishes a reverberating negative feedback cycle in which progressive endothelial dysfunction and disturbances in glucose and lipid metabolism develop secondary to the insulin resistance. Vascular damage, which results from lipid deposition and oxidative stress to the vessel wall, triggers an inflammatory reaction, and the release of chemoattractants and cytokines worsens the insulin resistance and endothelial dysfunction.From the clinical standpoint, much experimental evidence supports the concept that therapies that improve insulin resistance and endothelial dysfunction reduce cardiovascular morbidity and mortality. Moreover, interventional strategies that reduce insulin resistance ameliorate endothelial dysfunction, while interventions that improve tissue sensitivity to insulin enhance vascular endothelial function. There is general agreement that aggressive therapy aimed simultaneously at improving insulin-mediated glucose/lipid metabolism and endothelial dysfunction represents an important strategy in preventing/delaying the appearance of atherosclerosis. Interventions that 1 correct carbohydrate and lipid metabolism, 2 improve insulin resistance, 3 reduce blood pressure and restore vascular reactivity, and 4 attenuate procoagulant and inflammatory responses in adults with a high risk of developing cardiovascular disease reduce cardiovascular morbidity and mortality. Whether these benefits hold when the same prevention strategies are applied to younger, high-risk individuals remains to be determined.
The impact of insulin resistance on endothelial function, progenitor cells and repair
Richard M Cubbon
The Academic Unit of Cardiovascular Medicine, The LIGHT Laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
Adil Rajwani
The Academic Unit of Cardiovascular Medicine, The LIGHT Laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
Stephen B Wheatcroft
The Academic Unit of Cardiovascular Medicine, The LIGHT Laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
Abstract
The structural and functional integrity of the vascular endothelium plays a critical role in vascular homeo-stasis. Insulin resistance, an important risk factor for cardiovascular disease, is thought to promote atherosclerosis through a reciprocal relationship with endothelial dysfunction. In health, cumulative damage to endothelial cells incurred by exposure to risk factors is mitigated by endogenous reparative processes. Disruption of the balance between endothelial damage and repair may mediate atherosclerotic progression. Bone marrow-derived ‘endothelial progenitor cells' (EPC) have been identified as significant contributors to endogenous vascular repair. Insulin resistance is associated with a spectrum of biochemical abnormalities which have the potential to reduce the availability of EPCs and diminish their capacity for vascular repair. Many lifestyle and pharmacological interventions which improve insulin resistance also increase the numbers and functionality of EPCs. Cell-based therapies may also hold promise for the prevention and treatment of cardiovascular disease.
Basic Science for Clinicians
Reciprocal Relationships Between Insulin Resistance and Endothelial Dysfunction
Molecular and Pathophysiological Mechanisms
Jeong-a Kim, PhD;
Monica Montagnani, MD, PhD;
Kwang Kon Koh, MD;
Michael J. Quon, MD, PhD
+ Author Affiliations
From the Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Md (J.K., M.J.Q.); Department of Pharmacology and Human Physiology, Section of Pharmacology, University of Bari Medical School, Bari, Italy (M.M.); and the Division of Cardiology, Gil Heart Center, Gachon Medical School, Incheon, Korea (K.K.K.).
Correspondence to Michael J. Quon, MD, PhD, Chief, Diabetes Unit, NCCAM, NIH, 10 Center Dr, Building 10, Room 6C-205, Bethesda, MD 20892-1632. E-mail
quonm@nih.gov
Abstract
Endothelial dysfunction contributes to cardiovascular diseases, including hypertension, atherosclerosis, and coronary artery disease, which are also characterized by insulin resistance. Insulin resistance is a hallmark of metabolic disorders, including type 2 diabetes mellitus and obesity, which are also characterized by endothelial dysfunction. Metabolic actions of insulin to promote glucose disposal are augmented by vascular actions of insulin in endothelium to stimulate production of the vasodilator nitric oxide (NO). Indeed, NO-dependent increases in blood flow to skeletal muscle account for 25% to 40% of the increase in glucose uptake in response to insulin stimulation. Phosphatidylinositol 3-kinase–dependent insulin-signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. Other distinct nonmetabolic branches of insulin-signaling pathways regulate secretion of the vasoconstrictor endothelin-1 in endothelium. Metabolic insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase–dependent signaling, which in endothelium may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. Therapeutic interventions in animal models and human studies have demonstrated that improving endothelial function ameliorates insulin resistance, whereas improving insulin sensitivity ameliorates endothelial dysfunction. Taken together, cellular, physiological, clinical, and epidemiological studies strongly support a reciprocal relationship between endothelial dysfunction and insulin resistance that helps to link cardiovascular and metabolic diseases. In the present review, we discuss pathophysiological mechanisms, including inflammatory processes, that couple endothelial dysfunction with insulin resistance and emphasize important therapeutic implications.
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