Research Blog

July 16, 2021

Endothelial Dysfunction part 10 - 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:

The Endothelial Dysfunction Series

  1. Endothelial Dysfunction - An Overview
  2. Endothelial Dysfunction - The Endothelium
  3. Endothelial Dysfunction - Nitric Oxide
  4. Endothelial Dysfunction - Diseases and Causes
  5. Endothelial Dysfunction - Immune Response & Oxidative Stress
  6. Endothelial Dysfunction  & Atherosclerosis
  7. Endothelial Dysfunction - Assessment Part 1
  8. Endothelial Dysfunction - Assessment part 2
  9. Endothelial Dysfunction - Functional Naturopathic Approach
  10. Endothelial Dysfunction part 10 - Optimal Takeaways

  • 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 

Tag(s): Conditions

Other posts you might be interested in