Allopathic approaches to endothelial dysfunction are based on its identification once established versus early prevention. Functional approaches to endothelial dysfunction rely on recognition of contributing factors and early assessment of related biomarkers.
Functional approaches to endothelial dysfunction rely on recognition of contributing factors and early assessment of related biomarkers.
Early stages of endothelial dysfunction may be reversible before full progression to atherosclerosis.[5]
Major modifiable factors contributing to endothelial dysfunction include unhealthy diet (inflammatory, processed foods, low in micronutrients, antioxidants, phytonutrients, fiber, omega-3s, monounsaturated fats); exposure to cigarette smoke, toxins, and pollution; excess inflammatory compounds and oxidative stress; nutrient insufficiencies; and sedentary lifestyle. Assessing these factors should be the first step in evaluating risk of atherosclerosis and endothelial dysfunction.
Remember, unbridled oxidative stress and inflammation disrupt nitric oxide metabolism and promote endothelial dysfunction. They must be addressed to order to rein in this potentially debilitating condition:[6]
It is likely that excess inflammation from any source, even periodontitis or arthritis, can cause damage to the vascular endothelium so a full history is essential.[7]
The functional, naturopathic approach to endothelial dysfunction is recognition of its causes and mitigation of their effects. Early recognition of oxidative stress risk and detection of endothelial dysfunction is critical to reversing or preventing atherosclerosis and its progression to CVD.[8]
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Source: Widmer, R Jay, and Amir Lerman. “Endothelial dysfunction and cardiovascular disease.” Global cardiology science & practice vol. 2014,3 291-308. 16 Oct. 2014, doi:10.5339/gcsp.2014.43 This is an open access article distributed under the terms of the Creative Commons Attribution license CC BY 4.0, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
Source: Upadhyay, Ravi Kant. “Emerging risk biomarkers in cardiovascular diseases and disorders.” Journal of lipids vol. 2015 (2015): 971453. doi:10.1155/2015/971453 This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Continued exposure to cardiovascular risk factors is mirrored in pathological changes to blood vessels. Loss of integrity of the vascular endothelium is accompanied by increased smooth muscle cell migration and proliferation, leukocyte migration, and adhesion.[9]
Successive progression of transient ischemic attack and chronic heart failure in man.
Source: Upadhyay, Ravi Kant. “Emerging risk biomarkers in cardiovascular diseases and disorders.” Journal of lipids vol. 2015 (2015): 971453. doi:10.1155/2015/971453 This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Meta-analysis indicates that endothelial function is typically compromised in adults following a high-fat mixed meal and that the observed impairment in brachial artery flow-mediated dilation is a sign of cardiovascular risk, morbidity and mortality. Researchers investigated whether adolescents would demonstrate similar changes in post-prandial flow mediated dilation.
A small study of 10 adolescents observed that a high-fat meal also high in protein did not significantly impair arterial dilation in the same way a high-fat diet was expected to. Also, addition of insoluble wheat fiber to a high-fat meal blunted post-prandial hypertriglyceridemia and related changes in flow-mediated arterial dilation. Researchers recommend conducting larger studies to investigate these relationships further.[10]
A high-fat Western-style diet can impair endothelial function for up to four hours. To investigate mitigation of this threat, a randomized, double-blind, placebo-controlled study of phytonutrient supplementation in 38 healthy adult volunteers was conducted.
Results indicated that daily supplementation with fruit and vegetable concentrates, including those enhanced with antioxidant nutrients, significantly improved flow-mediated vasodilation using the brachial artery reactivity test (BART) following a high-fat fast food meal containing 50 grams of fat.
In the supplement group, serum total and LDL cholesterol decreased significantly, and serum levels of nitric oxide metabolites increased significantly.[11]
This study followed up the observation that supplementation with antioxidants vitamin C and vitamin E prevented the significant reduction in vasodilation that occurs following a high-fat meal.[12]
Phytonutrients/phytochemicals are compounds unique to plant-based foods. Many of them have antioxidant and anti-inflammatory benefits.
Abundant intake of fruits, vegetables, phytonutrients, and antioxidants is closely associated with optimal health, including reduction of cardiovascular risk factors. Research demonstrates that phytonutrients and antioxidants can exert positive effects on endothelial function, including its generation of nitric oxide. These positive effects are not new news, they just seem to have been forgotten in the medical models that have been developed.
Omega-3 fatty acids can have a vasoprotective effect in endothelial dysfunction as demonstrated in a number of studies in those with metabolic syndrome, elevated BMI, hyperlipidemia, and those who smoked cigarettes. A benefit of omega-3 intake in in diabetics was also observed in two of five studies reviewed. Specific vasoprotective effects of omega-3 fatty acids include:[13]
Adherence to a healthy diet is essential to addressing atherosclerosis and endothelial dysfunction. However, supplementation may be beneficial as well, especially considering that micronutrient deficiencies are common among the general population but even more common in those with hypertension, cardiovascular disease, environmental toxin exposure, and prescription drug use.[17]
Nutrition supplementation can significantly improve endothelial function as evidenced by a number of clinical studies.
Vitamin C (ascorbate/ascorbic acid) is of particular interest due to its potent antioxidant activity as a free radical scavenger and the fact that humans cannot synthesize ascorbate while most mammals can.
Arginine supplementation may also be of specific benefit in endothelial dysfunction.
A variety of nutrients are found to have antihypertensive effects, therefore reducing stress and further damage to the vascular endothelium. These include: [26]
Coenzyme Q10 is produced endogenously though its production is impaired by HMG-CoA reductase inhibitors (statin drugs). Supplementation with 150 mg of CoQ10 per day can support antioxidant function, reduce inflammatory IL-6, and reduce oxidative stress in those with coronary artery disease.[27]
A randomized, double-blind, controlled study of 20 individuals with advanced atherosclerosis and CAD indicated that supplementation with 10 mg of melatonin was associated with a significant decrease in mean levels of ICAM, VCAM, and CRP, and a significant increase in nitric oxide.[28]
Preliminary research suggests a role for cobalamin as a cofactor in the metabolism of nitric oxide. Researchers propose that the intermediate glutathionyl-cobalamin is an active form of B12 that participates in production and function of nitric oxide and in turn effects cell membrane protection, immune, and vascular health.[29]
A meta-analysis of 16 studies indicated that supplementation with pomegranate juice had a significant effect on inflammatory markers hs-CRP, IL-6, and TNF-alpha.[30]
Dark Chocolate
Dark chocolate (high in flavonoids and antioxidant factors) significantly improved endothelial-dependent coronary vascular function, reduced oxidative stress, and reduced platelet adhesion in 22 heart transplant patients.[31]
Though a topic unto itself, physical activity and exercise can improve endothelial function… no surprise there![32]
Animal and human research support the application of regular, robust physical activity to support cardiovascular and endothelial function. A minimum of 40 minutes of physical activity at least 3 days per week is recommended. Optimal activity includes 10,000 steps per day and engagement in aerobic activity 3 days per week.[33]
NEXT UP - Endothelial Dysfunction part 10 - The Optimal Takeaways
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[2] Hirata, Yasunobu et al. “Diagnosis and treatment of endothelial dysfunction in cardiovascular disease.” International heart journal vol. 51,1 (2010): 1-6.
[3] Miller, Mark R. “Oxidative stress and the cardiovascular effects of air pollution.” Free radical biology & medicine vol. 151 (2020): 69-87.
[4] Cedars Sinai Women’s Heart Center. Endothelial Function Testing
[5] Park, Kyoung-Ha, and Woo Jung Park. “Endothelial Dysfunction: Clinical Implications in Cardiovascular Disease and Therapeutic Approaches.” Journal of Korean medical science vol. 30,9 (2015): 1213-25.
[6] Widmer, R Jay, and Amir Lerman. “Endothelial dysfunction and cardiovascular disease.” Global cardiology science & practice vol. 2014,3 291-308. 16 Oct. 2014.
[7] Stone, William L., et al. “Pathology, Inflammation.” StatPearls, StatPearls Publishing, 27 August 2020.
[8] Park, Kyoung-Ha, and Woo Jung Park. “Endothelial Dysfunction: Clinical Implications in Cardiovascular Disease and Therapeutic Approaches.” Journal of Korean medical science vol. 30,9 (2015): 1213-25.
[9] Park, Kyoung-Ha, and Woo Jung Park. “Endothelial Dysfunction: Clinical Implications in Cardiovascular Disease and Therapeutic Approaches.” Journal of Korean medical science vol. 30,9 (2015): 1213-25.
[10] Whisner, Corrie M et al. “Effects of Low-Fat and High-Fat Meals, with and without Dietary Fiber, on Postprandial Endothelial Function, Triglyceridemia, and Glycemia in Adolescents.” Nutrients vol. 11,11 2626. 2 Nov. 2019.
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[12] Plotnick, G D et al. “Effect of antioxidant vitamins on the transient impairment of endothelium-dependent brachial artery vasoactivity following a single high-fat meal.” JAMA vol. 278,20 (1997): 1682-6.
[13] Zehr, Kayla R, and Mary K Walker. “Omega-3 polyunsaturated fatty acids improve endothelial function in humans at risk for atherosclerosis: A review.” Prostaglandins & other lipid mediators vol. 134 (2018): 131-140.
[14] Su, Jin Bo. “Vascular endothelial dysfunction and pharmacological treatment.” World journal of cardiology vol. 7,11 (2015): 719-41.
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[20] Plantinga, Yvonne et al. “Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients.” American journal of hypertension vol. 20,4 (2007): 392-7.
[21] Engler, Marguerite M et al. “Antioxidant vitamins C and E improve endothelial function in children with hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial.” Circulation vol. 108,9 (2003): 1059-63.
[22] Gornik, Heather L, and Mark A Creager. “Arginine and endothelial and vascular health.” The Journal of nutrition vol. 134,10 Suppl (2004): 2880S-2887S; discussion 2895S.
[23] Morris, Sidney M Jr. “Arginine: beyond protein.” The American journal of clinical nutrition vol. 83,2 (2006): 508S-512S.
[24] Widmer, R Jay, and Amir Lerman. “Endothelial dysfunction and cardiovascular disease.” Global cardiology science & practice vol. 2014,3 291-308. 16 Oct. 2014.
[25] Menzel, Daniel et al. “L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation.” European journal of nutrition vol. 57,2 (2018): 557-568.
[26] Houston, Mark. “The role of nutrition and nutraceutical supplements in the treatment of hypertension.” World journal of cardiology vol. 6,2 (2014): 38-66.
[27] Bronzato, Sofia, and Alessandro Durante. “Dietary Supplements and Cardiovascular Diseases.” International journal of preventive medicine vol. 9 80. 17 Sep. 2018.
[28] Javanmard, Shaghayegh Haghjooy et al. “The effect of melatonin on endothelial dysfunction in patient undergoing coronary artery bypass grafting surgery.” Advanced biomedical research vol. 5 174. 28 Nov. 2016.
[29] Paul, Cristiana, and David M Brady. “Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms.” Integrative medicine (Encinitas, Calif.) vol. 16,1 (2017): 42-49.
[30] Wang, Peng et al. “The effects of pomegranate supplementation on biomarkers of inflammation and endothelial dysfunction: A meta-analysis and systematic review.” Complementary therapies in medicine vol. 49 (2020): 102358.
[31] Flammer, Andreas J et al. “Dark chocolate improves coronary vasomotion and reduces platelet reactivity.” Circulation vol. 116,21 (2007): 2376-82.
[32] Barthelmes, Jens et al. “Endothelial dysfunction in cardiovascular disease and Flammer syndrome-similarities and differences.” The EPMA journal vol. 8,2 99-109. 6 Jun. 2017.
[33] Bender, Shawn B, and M Harold Laughlin. “Modulation of endothelial cell phenotype by physical activity: impact on obesity-related endothelial dysfunction.” American journal of physiology. Heart and circulatory physiology vol. 309,1 (2015): H1-8.