Endothelial Dysfunction - The Optimal Takeaways

Endothelial Dysfunction - The Optimal Takeaways

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

The early intervention and prevention of endothelial dysfunction includes the following:

  • An optimal flow-mediated dilation (FMD) reading, a reflection of nitric oxide production
  • A healthy diet rich in fresh fruits and vegetables, antioxidants, omega-3 fatty acids, monounsaturated fats, anti-inflammatory herbs and spices, vitamins, minerals, and phytonutrients
  • Targeted nutrition supplementation
  • Minimization of exposure to toxins, pollution, cigarette smoke, and stress
  • Regular robust physical activity
  • Maintain a desirable body weight and lean body mass
  • Stress management
  • Address biomarkers out of the optimal range including those related to oxidative stress, inflammation, and blood glucose regulation:


  • Homocysteine
  • Blood glucose
  • Fibrinogen
  • C-reactive protein (CRP, hs-CRP)
  • Iron levels
  • Neutrophil:Lymphocyte Ratio (NLR)
  • Oxidized LDL (OxLDL)
  • Asymmetric dimethylarginine (ADMA)
  • Myeloperoxidase (MPO)
  • Malondialdehyde (MDA)
  • Gamma-glutamyl transferase (GGT)


  • Omega-3 Index
  • Adiponectin
  • Testosterone

Overview - Optimal Takeaways

  • The vascular endothelium is considered the largest endocrine organ in the body.
  • It signals underlying smooth muscle to constrict and relax and protects it from toxins and oxidative stress.
  • The vascular endothelium regulates a wide variety of metabolic activities including thrombosis, inflammation, leukocyte adhesion, vasomotor tone, blood flow, and blood vessel constriction and relaxation.
  • Cardiovascular disease is the primary cause of death worldwide… and endothelial dysfunction is the primary cause of CVD and an underlying contributor to diabetes and hypertension.
  • Causes of endothelial dysfunction overlap with those of atherosclerosis CVD and include immune activation, pro-inflammatory cytokines, oxidative stress, hyperglycemia, toxin exposure, pollution, homocysteine, poor diet, sedentary lifestyle, etc.
  • Nitric oxide helps to maintain reduced vascular tension and low oxidative stress, conditions required for healthy blood vessels. Disruption of nitric oxide metabolism causes a disruption of the vascular endothelium.

Dysfunction - Optimal Takeaways

  • Immune activation and immune cell infiltration can promote endothelial dysfunction, especially neutrophil activity.
  • Oxidative stress is a significant contributor to endothelial dysfunction due to increased free radicals and oxidized LDL, and decreased superoxide dismutase and nitric oxide bioavailability.
  • Endothelial dysfunction leads to atherosclerosis, a culmination of antioxidant insufficiency, oxidative stress, chronic inflammation, elevated homocysteine, and undesirable lifestyle factors.
  • Pollution and particulate matter contribute to endothelial dysfunction.
  • Early detection of endothelial dysfunction is critical to preventing atherosclerosis and CVD.

Assessment - Optimal Takeaways

  • Endothelial dysfunction itself may not have overt symptoms, and atherosclerosis has a “silent phase” and can go undetected until telltale signs such as angina occur.
  • Clinical measurement of endothelial dysfunction may be achieved through a variety of techniques, with flow-mediated dilation (FMD) being the most common tool.
  • FMD reflects nitric oxide production and can be instrumental in predicting CVD events in seemingly low-risk individuals.
  • The “cold pressor test” is a non-invasive method of evaluating the sympathetic-mediated release of nitric oxide. In endothelial dysfunction, vasoconstriction occurs and hyperreactors will mount a hypertensive response.
  • Biomarker characteristics of endothelial dysfunction include:
    • Elevated homocysteine, glucose, fibrinogen, CRP/hs-CRP, iron, ferritin, neutrophil:lymphocyte ratio, oxidized LDL, asymmetric dimethylarginine, myeloperoxidase, malondialdehyde, gamma-glutamyl transferase, and increased inflammatory markers.
    • Insufficient testosterone, low omega-3 index, low adiponectin
    • Advanced biomarkers may also be measured (e.g., cellular adhesion molecules, von Willebrand factor, sNOX2-dp, 8-isoPFG2a, EPCs, MVs)

Treatment - Optimal Takeaways

  • Hypertension, diabetes, obesity, hyperlipidemia, and smoking are risk factors for thrombosis, atherosclerosis, and endothelial dysfunction.[i]
  • Combined with oxidative stress and a pro-inflammatory milieu, these risk factors form the main pillars underlying cardiovascular risk.
  • Major modifiable factors include diet, activity, lifestyle, nutrient insufficiencies, supplementation, exposure to toxins and pollutants, and stress management.
  • Failure to address these factors will propel individuals down the road from metabolic disturbance to chronic, life-threatening disease.
  • Basically, a healthy lifestyle makes for a healthy life.
  • Allopathic treatments are based on identification of endothelial dysfunction once it occurs instead of early preventative measures.
  • Functional naturopathic approaches to endothelial dysfunction rely on recognizing and addressing contributing factors and associated biomarkers.


[i] Qi, Haozhe et al. “Neutrophil Extracellular Traps and Endothelial Dysfunction in Atherosclerosis and Thrombosis.” Frontiers in immunology vol. 8 928. 7 Aug. 2017, doi:10.3389/fimmu.2017.00928 [R] This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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